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Review Articles

The environment and male reproductive system: the potential role and underlying mechanisms of cadmium in testis cancer

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Pages 412-435 | Received 30 Jan 2023, Accepted 15 Aug 2023, Published online: 22 Sep 2023

References

  • Al-Bader A, Omu AE, Dashti H. 1999. Chronic cadmium toxicity to sperm of heavy cigarette smokers: immunomodulation by zinc. Arch Androl. 43(2):135–140. doi: 10.1080/014850199262643.
  • Albers PA, W; Algaba F, Bokemeyer C, Cohn-Cedermark G, Fizazi K, Horwich A, Laguna MP, Nicolai N, Oldenburg J. 2018. Testicular cancer. EAU Guidelines. http://uroweb.org/guideline/testicular-cancer/.
  • Amara S, Abdelmelek H, Garrel C, Guiraud P, Douki T, Ravanat JL, Favier A, Sakly M, Ben Rhouma K. 2008. Preventive effect of zinc against cadmium-induced oxidative stress in the rat testis. J Reprod Dev. 54(2):129–134. doi: 10.1262/jrd.18110.
  • Anetor JI. 2012. Rising environmental cadmium levels in developing countries: threat to genome stability and health. Niger J Physiol Sci. 27(2):103–115.
  • Aoki A, Hoffer AP. 1978. Reexamination of the lesions in rat testis caused by cadmium. Biol Reprod. 18(4):579–591. doi: 10.1095/biolreprod18.4.579.
  • ATSDR. 2012. Toxicological profile for cadmium 2012. Toxicological profiles. Agency for Toxic Substances and Disease Registry.
  • Benbrahim-Tallaa L, Waterland RA, Dill AL, Webber MM, Waalkes MP. 2007. Tumor suppressor gene inactivation during cadmium-induced malignant transformation of human prostate cells correlates with overexpression of de novo DNA methyltransferase. Environ Health Perspect. 115(10):1454–1459. doi: 10.1289/ehp.10207.
  • Bertin G, Averbeck D. 2006. Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie. 88(11):1549–1559. doi: 10.1016/j.biochi.2006.10.001.
  • Bhave MR, Wilson MJ, Waalkes MP. 1988. Methylation status and organization of the metallothionein-I gene in livers and testes of strains of mice resistant and susceptible to cadmium. Toxicology. 50(3):231–245. doi: 10.1016/0300-483x(88)90041-8.
  • Bialkowski K, Bialkowska A, Kasprzak KS. 1999. Cadmium(II), unlike nickel(II), inhibits 8-oxo-dGTPase activity and increases 8-oxo-dG level in DNA of the rat testis, a target organ for cadmium(II) carcinogenesis. Carcinogenesis. 20(8):1621–1624. doi: 10.1093/carcin/20.8.1621.
  • Blanco A, Moyano R, Molina Lopez AM, Blanco C, Flores-Acuna R, Garcia-Flores JR, Espada M, Monterde JG. 2010. Preneoplastic and neoplastic changes in the Leydig cells population in mice exposed to low doses of cadmium. Toxicol Ind Health. 26(8):451–457. doi: 10.1177/0748233710371111.
  • Bomhard E, Vogel O, Loser E. 1987. Chronic effects on single and multiple oral and subcutaneous cadmium administrations on the testes of Wistar rats. Cancer Lett. 36(3):307–315. doi: 10.1016/0304-3835(87)90024-3.
  • Boorman GA, Waalkes MP, Elwell MR, Eustis SL. 1987. Seminoma, testis, rat. In: Jones TC, and Hunt RD, editors. Monographs on pathology of laboratory animals, genital system. Berlin: Springer-Verlag; p. 192–195.
  • Bosl GJ, Motzer RJ. 1997. Testicular germ-cell cancer. N Engl J Med. 337(4):242–253. doi: 10.1056/NEJM199707243370406.
  • Bray F, Jemal A, Grey N, Ferlay J, Forman D. 2012. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol. 13(8):790–801. doi: 10.1016/S1470-2045(12)70211-5.
  • Brocato J, Costa M. 2013. Basic mechanics of DNA methylation and the unique landscape of the DNA methylome in metal-induced carcinogenesis. Crit Rev Toxicol. 43(6):493–514. doi: 10.3109/10408444.2013.794769.
  • Brown CE, Warren S, Chute RN, Ryan KJ, Todd RB. 1979. Hormonally induced tumors of the reproductive system of parabiosed male rats. Cancer Res. 39(10):3971–3976.
  • Bruning T, Pesch B, Wiesenhutter B, Rabstein S, Lammert M, Baumuller A, Bolt HM. 2003. Renal cell cancer risk and occupational exposure to trichloroethylene: results of a consecutive case-control study in Arnsberg, Germany. Am J Ind Med. 43(3):274–285. doi: 10.1002/ajim.10185.
  • Bulat ZP, Djukic-Cosic D, Malicevic Z, Bulat P, Matovic V. 2008. Zinc or magnesium supplementation modulates cd intoxication in blood, kidney, spleen, and bone of rabbits. Biol Trace Elem Res. 124(2):110–117. doi: 10.1007/s12011-008-8128-5.
  • Burukoğlu D, Bayçu C. 2008. Protective effects of zinc on testes of cadmium-treated rats. Bull Environ Contam Toxicol. 81(6):521–524. doi: 10.1007/s00128-007-9211-x.
  • Carmignani L, Gadda F, Mancini M, Gazzano G, Nerva F, Rocco F, Colpi GM. 2004. Detection of testicular ultrasonographic lesions in severe male infertility. J Urol. 172(3):1045–1047. doi: 10.1097/01.ju.0000134892.10525.39.
  • Chen YC, Pu YS, Wu HC, Wu TT, Lai MK, Yang CY, Sung FC. 2009. Cadmium burden and the risk and phenotype of prostate cancer. BMC Cancer. 9(1):429. doi: 10.1186/1471-2407-9-429.
  • Chia VM, Quraishi SM, Devesa SS, Purdue MP, Cook MB, McGlynn KA. 2010. International trends in the incidence of testicular cancer, 1973-2002. Cancer Epidemiol Biomarkers Prev. 19(5):1151–1159. doi: 10.1158/1055-9965.EPI-10-0031.
  • Cook JC, Klinefelter GR, Hardisty JF, Sharpe RM, Foster PM. 1999. Rodent Leydig cell tumorigenesis: a review of the physiology, pathology, mechanisms, and relevance to humans. Crit Rev Toxicol. 29(2):169–261. doi: 10.1080/10408449991349203.
  • Cook JC, Mullin LS, Frame SR, Biegel LB. 1993. Investigation of a mechanism for Leydig cell tumorigenesis by linuron in rats. Toxicol Appl Pharmacol. 119(2):195–204. doi: 10.1006/taap.1993.1060.
  • Dalton TP, He L, Wang B, Miller ML, Jin L, Stringer KF, Chang X, Baxter CS, Nebert DW. 2005. Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis. Proc Natl Acad Sci U S A. 102(9):3401–3406. doi: 10.1073/pnas.0406085102.
  • Danielsson BR, Dencker L, Lindgren A, Tjalve H. 1984. Accumulation of toxic metals in male reproduction organs. Arch Toxicol Suppl. 7:177–180.
  • de Angelis C, Galdiero M, Pivonello C, Salzano C, Gianfrilli D, Piscitelli P, Lenzi A, Colao A, Pivonello R. 2017. The environment and male reproduction: the effect of cadmium exposure on reproductive function and its implication in fertility. Reprod Toxicol. 73:105–127. doi: 10.1016/j.reprotox.2017.07.021.
  • Deagen JT, Whanger PD. 1985. Properties of cadmium-binding proteins in rat testes. Characteristics unlike metallothionein. Biochem J. 231(2):279–283. doi: 10.1042/bj2310279.
  • Filipic M. 2012. Mechanisms of cadmium induced genomic instability. Mutat Res. 733(1-2):69–77.
  • Filipic M, Hei TK. 2004. Mutagenicity of cadmium in mammalian cells: implication of oxidative DNA damage. Mutat Res. 546(1-2):81–91. doi: 10.1016/j.mrfmmm.2003.11.006.
  • Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, Chimed-Orchir O, Dandona R, Dandona L, Global Burden of Disease Cancer, et al. 2016. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 3(4):524–548.
  • Fox MR, Tao SH, Stone CL, Fry BE. Jr 1984. Effects of zinc, iron and copper deficiencies on cadmium in tissues of Japanese quail. Environ Health Perspect. 54:57–65. doi: 10.1289/ehp.845457.
  • Fujishiro H, Okugaki S, Yasumitsu S, Enomoto S, Himeno S. 2009. Involvement of DNA hypermethylation in down-regulation of the zinc transporter ZIP8 in cadmium-resistant metallothionein-null cells. Toxicol Appl Pharmacol. 241(2):195–201. doi: 10.1016/j.taap.2009.08.015.
  • Godt J, Scheidig F, Grosse-Siestrup C, Esche V, Brandenburg P, Reich A, Groneberg DA. 2006. The toxicity of cadmium and resulting hazards for human health. J Occup Med Toxicol. 1(1):22. doi: 10.1186/1745-6673-1-22.
  • Greene MH, Kratz CP, Mai PL, Mueller C, Peters JA, Bratslavsky G, Ling A, Choyke PM, Premkumar A, Bracci J, et al. 2010. Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype. Endocr Relat Cancer. 17(2):R109–121. doi: 10.1677/ERC-09-0254.
  • Grollman AP, Moriya M. 1993. Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet. 9(7):246–249. doi: 10.1016/0168-9525(93)90089-z.
  • Gunn SAGTC. 1970. Cadmium and health: a toxicological and epidemiological appraisal. In: The testis. New York: Academic Press; 3.
  • Gunn SA, Gould TC, Anderson WA. 1963a. Cadmium-induced interstitial cell tumors in rats and mice and their prevention by zinc. J Natl Cancer Inst. 31:745–759.
  • Gunn SA, Gould TC, Anderson WA. 1963b. The selective injurious response of testicular and epididymal blood vessels to cadmium and its prevention by zinc. Am J Pathol. 42(6):685–702.
  • Gunn SA, Gould TC, Anderson WA. 1964. Effect of zinc on cancerogenesis by cadmium. Proc Soc Exp Biol Med. 115(3):653–657. doi: 10.3181/00379727-115-28996.
  • Gunn SA, Gould TC, Anderson WA. 1965. Comparative study of interstitial cell tumors of rat testis induced by cadmium injection and vascular ligation. J Natl Cancer Inst. 35(2):329–337.
  • Gunn SA, Gould TC, Anderson WA. 1966. Loss of selective injurious vascular response to cadmium in regenerated blood vessels of testis. Am J Pathol. 48(6):959–969.
  • Hasle H, Mellemgaard A, Nielsen J, Hansen J. 1995. Cancer incidence in men with Klinefelter syndrome. Br J Cancer. 71(2):416–420. doi: 10.1038/bjc.1995.85.
  • Heller CG, Leach DR. 1971. Quantification of Leydig cells and measurement of Leydig-cell size following administration of human chorionic gonadotrophin to normal men. J Reprod Fertil. 25(2):185–192. doi: 10.1530/jrf.0.0250185.
  • Hengstler JG, Bolm-Audorff U, Faldum A, Janssen K, Reifenrath M, Gotte W, Jung D, Mayer-Popken O, Fuchs J, Gebhard S, et al. 2003. Occupational exposure to heavy metals: DNA damage induction and DNA repair inhibition prove co-exposures to cadmium, cobalt and lead as more dangerous than hitherto expected. Carcinogenesis. 24(1):63–73. doi: 10.1093/carcin/24.1.63.
  • Hofmann M, Schlegel PG, Hippert F, Schmidt P, von-Schweinitz D, Leuschner I, Gobel U, Calaminus G, Schneider DT, M. S. Group. 2013. Testicular sex cord stromal tumors: analysis of patients from the MAKEI study. Pediatr Blood Cancer. 60(10):1651–1655. doi: 10.1002/pbc.24607.
  • Hu J, Mao Y, White K. 2002. Renal cell carcinoma and occupational exposure to chemicals in Canada. Occup Med (Lond). 52(3):157–164. doi: 10.1093/occmed/52.3.157.
  • IARC. 2012. IARC Monographs vol. 100C Evaluation of carcinogenic risks to humans. Lyon (France): International Agency for Research on Cancer; 100 C.
  • IARC. 2018. Agents classified by the IARC monographs. Lyon (France): IARC.
  • Idrees MT, Ulbright TM, Oliva E, Young RH, Montironi R, Egevad L, Berney D, Srigley JR, Epstein JI, Tickoo SK, Members of the International Society of Urological Pathology Testicular Tumour Panel. 2017. The WHO 2016 classification of testicular non-germ cell tumours: a review and update from the international society of urological pathology testis consultation panel. Histopathology. 70(4):513–521. doi: 10.1111/his.13115.
  • Isidori AM, Pozza C, Gianfrilli D, Giannetta E, Lemma A, Pofi R, Barbagallo F, Manganaro L, Martino G, Lombardo F, et al. 2014. Differential diagnosis of nonpalpable testicular lesions: qualitative and quantitative contrast-enhanced US of benign and malignant testicular tumors. Radiology. 273(2):606–618. doi: 10.1148/radiol.14132718.
  • Ito T, Sawauchi K. 1966. Inhibitory effects on cadmium-induced testicular damage by pretreatment with smaller cadmium dose. Okajimas Folia Anat Jpn. 42(2):107–117. doi: 10.2535/ofaj1936.42.2-3_107.
  • Jacobs BB, Huseby RA. 1967. Neoplasms occurring in aged Fischer rats, with special reference to testicular, uterine, and thyroid tumors. J Natl Cancer Inst. 39(2):303–309.
  • Jockenhovel JK, Rutgers JS, Mason JE, Griffin, RS, Swerdloff. 1993. Leydig cell neoplasia in a patient with Reifenstein syndrome. Exp Clin Endocrinol. 101(6):365–370.
  • Julin B, Wolk A, Johansson JE, Andersson SO, Andren O, Akesson A. 2012. Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study. Br J Cancer. 107(5):895–900. doi: 10.1038/bjc.2012.311.
  • Kagi JH, Schaffer A. 1988. Biochemistry of metallothionein. Biochemistry. 27(23):8509–8515.
  • Kasprzak KS, Bialkowski K. 2000. Inhibition of antimutagenic enzymes, 8-oxo-dGTPases, by carcinogenic metals. Recent developments. J Inorg Biochem. 79(1-4):231–236. doi: 10.1016/s0162-0134(99)00240-8.
  • Kasprzak KS, Waalkes MP, Poirier LA. 1987. Effects of essential divalent metals on carcinogenicity and metabolism of nickel and cadmium. Biol Trace Elem Res. 13(1):253–273. doi: 10.1007/BF02796637.
  • Kauppinen T, Heikkila P, Plato N, Woldbaek T, Lenvik K, Hansen J, Kristjansson V, Pukkala E. 2009. Construction of job-exposure matrices for the Nordic Occupational Cancer Study (NOCCA). Acta Oncol. 48(5):791–800. doi: 10.1080/02841860902718747.
  • Kauppinen T, Toikkanen J, Pukkala E. 1998. From cross-tabulations to multipurpose exposure information systems: a new job-exposure matrix. Am J Ind Med. 33(4):409–417. doi: 10.1002/(SICI)1097-0274(199804)33:4<409::AID-AJIM12>3.0.CO;2-2.
  • King LM, Banks WA, George WJ. 1999. Differences in cadmium transport to the testis, epididymis, and brain in cadmium-sensitive and -resistant murine strains 129/J and A/J. J Pharmacol Exp Ther. 289(2):825–830.
  • Kippler M, Engstrom K, Mlakar SJ, Bottai M, Ahmed S, Hossain MB, Raqib R, Vahter M, Broberg K. 2013. Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight. Epigenetics. 8(5):494–503. doi: 10.4161/epi.24401.
  • Klaassen CD, Liu J, Choudhuri S. 1999. Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol. 39(1):267–294. doi: 10.1146/annurev.pharmtox.39.1.267.
  • Li KY, Xiao WS, Wu Q, Chang XL, Zhou ZJ, Zhang J, Su DQ. 2009. Effect of neonatal exposure to environmental pollutants on the DNA methylation of rat testis. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 27(11):649–654.
  • Liu J, Corton C, Dix DJ, Liu Y, Waalkes MP, Klaassen CD. 2001. Genetic background but not metallothionein phenotype dictates sensitivity to cadmium-induced testicular injury in mice. Toxicol Appl Pharmacol. 176(1):1–9. doi: 10.1006/taap.2001.9262.
  • Liu Z, Li H, Soleimani M, Girijashanker K, Reed JM, He L, Dalton TP, Nebert DW. 2008. Cd2+ versus Zn2+ uptake by the ZIP8 HCO3–dependent symporter: kinetics, electrogenicity and trafficking. Biochem Biophys Res Commun. 365(4):814–820. doi: 10.1016/j.bbrc.2007.11.067.
  • McKenna IM, Bare RM, Waalkes MP. 1996. Metallothionein gene expression in testicular interstitial cells and liver of rats treated with cadmium. Toxicology. 107(2):121–130. doi: 10.1016/0300-483x(95)03252-b.
  • Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. 2016. The 2016 WHO classification of tumours of the urinary system and male genital organs-part a: renal, penile, and testicular tumours. Eur Urol. 70(1):93–105. doi: 10.1016/j.eururo.2016.02.029.
  • Mosharafa AA, Foster RS, Bihrle R, Koch MO, Ulbright TM, Einhorn LH, Donohue JP. 2003. Does retroperitoneal lymph node dissection have a curative role for patients with sex cord-stromal testicular tumors? Cancer. 98(4):753–757. doi: 10.1002/cncr.11573.
  • Murakami M, Hosokawa S, Yamada T, Harakawa M, Ito M, Koyama Y, Kimura J, Yoshitake A, Yamada H. 1995. Species-specific mechanism in rat Leydig cell tumorigenesis by procymidone. Toxicol Appl Pharmacol. 131(2):244–252. doi: 10.1006/taap.1995.1067.
  • Nebbioso A, Tambaro FP, Dell’Aversana C, Altucci L. 2018. Cancer epigenetics: moving forward. PLoS Genet. 14(6):e1007362. doi: 10.1371/journal.pgen.1007362.
  • Network NCCN. 2018. Testicular cancer NCCN evidence blocks. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). NCCNetwork.
  • Nordberg GF, Piscator M, Lind B. 1971. Distribution of cadmium among protein fractions of mouse liver. Acta Pharmacol Toxicol (Copenh). 29(5):456–470. doi: 10.1111/j.1600-0773.1971.tb00620.x.
  • Nordberg GF. 2009. Historical perspectives on cadmium toxicology. Toxicol Appl Pharmacol. 238(3):192–200. doi: 10.1016/j.taap.2009.03.015.
  • Oliveira H, Lopes T, Almeida T, Pereira MdL, Santos C. 2012. Cadmium-induced genetic instability in mice testis. Hum Exp Toxicol. 31(12):1228–1236. doi: 10.1177/0960327112445937.
  • Osbun N, Winters B, Holt SK, Schade GR, Lin DW, Wright JL. 2016. Characteristics of patients with sertoli and leydig cell testis neoplasms from a national population-based registry. Clin Genitourin Cancer. 15(2):e263–e266.
  • Parizek J. 1957. The destructive effect of cadmium ion on testicular tissue and its prevention by zinc. J Endocrinol. 15(1):56–63.
  • Pesch B, Haerting J, Ranft U, Klimpel A, Oelschlagel B, Schill W. 2000. Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study. Int J Epidemiol. 29(6):1014–1024. doi: 10.1093/ije/29.6.1014.
  • Pillai A, Gupta S. 2005. Antioxidant enzyme activity and lipid peroxidation in liver of female rats co-exposed to lead and cadmium: effects of vitamin E and Mn2+. Free Radic Res. 39(7):707–712. doi: 10.1080/10715760500092444.
  • Porter DW, Yakushiji H, Nakabeppu Y, Sekiguchi M, Fivash MJ, Jr., Kasprzak KS. 1997. Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II). Carcinogenesis. 18(9):1785–1791. doi: 10.1093/carcin/18.9.1785.
  • Pozza C, Gianfrilli D, Fattorini G, Giannetta E, Barbagallo F, Nicolai E, Cristini C, Di Pierro GB, Franco G, Lenzi A, et al. 2016. Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions. Andrology. 4(6):1193–1203. doi: 10.1111/andr.12260.
  • Prasad AS, Cossack ZT. 1982. Neutrophil zinc: an indicator of zinc status in man. Trans Assoc Am Physicians. 95:165–176.
  • Prüss-Ustün AW, J; Corvalán C, Bos R, Neira M. 2016. Preventing disease through healthy environments A global assessment of the burden of disease from environmental risks. Geneva (Switzerland): W. H. Organization.
  • Ray PD, Yosim A, Fry RC. 2014. Incorporating epigenetic data into the risk assessment process for the toxic metals arsenic, cadmium, chromium, lead, and mercury: strategies and challenges. Front Genet. 5:201. doi: 10.3389/fgene.2014.00201.
  • Reddy J, Svoboda D, Azarnoff D, Dawar R. 1973. Cadmium-induced Leydig cell tumors of rat testis: morphologic and cytochemical study. J Natl Cancer Inst. 51(3):891–903. doi: 10.1093/jnci/51.3.891.
  • Rehm S, Waalkes MP. 1988. Mixed Sertoli-Leydig cell tumor and rete testis adenocarcinoma in rats treated with CdCl2. Vet Pathol. 25(2):163–166. doi: 10.1177/030098588802500210.
  • Ren XY, Zhou Y, Zhang JP, Feng WH, Jiao BH. 2003. Expression of metallothionein gene at different time in testicular interstitial cells and liver of rats treated with cadmium. World J Gastroenterol. 9(7):1554–1558. doi: 10.3748/wjg.v9.i7.1554.
  • Ruiz-Hernandez A, Kuo CC, Rentero-Garrido P, Tang WY, Redon J, Ordovas JM, Navas-Acien A, Tellez-Plaza M. 2015. Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence. Clin Epigenetics. 7(1):55. doi: 10.1186/s13148-015-0055-7.
  • Sekiguchi M. 1996. MutT-related error avoidance mechanism for DNA synthesis. Genes Cells. 1(2):139–145. doi: 10.1046/j.1365-2443.1996.d01-232.x.
  • Setchell BP, Waites GM. 1970. Changes in the permeability of the testicular capillaries and of the ‘blood-testis barrier’ after injection of cadmium chloride in the rat. J Endocrinol. 47(1):81–86. doi: 10.1677/joe.0.0470081.
  • Shanmugalingam T, Soultati A, Chowdhury S, Rudman S, Van Hemelrijck M. 2013. Global incidence and outcome of testicular cancer. Clin Epidemiol. 5:417–427. doi: 10.2147/CLEP.S34430.
  • Shiraishi N, Hochadel JF, Coogan TP, Koropatnick J, Waalkes MP. 1995. Sensitivity to cadmium-induced genotoxicity in rat testicular cells is associated with minimal expression of the metallothionein gene. Toxicol Appl Pharmacol. 130(2):229–236. doi: 10.1006/taap.1995.1028.
  • Siegel RL, Miller KD, Jemal A. 2016. Cancer statistics, 2016. CA Cancer J Clin. 66(1):7–30. doi: 10.3322/caac.21332.
  • Silberstein JL, Bazzi WM, Vertosick E, Carver BS, Bosl GJ, Feldman DR, Bajorin DF, Motzer RJ, Al-Ahmadie H, Reuter VE, et al. 2014. Clinical outcomes of local and metastatic testicular sex cord-stromal tumors. J Urol. 192(2):415–419. doi: 10.1016/j.juro.2014.01.104.
  • Simpson BJ, Wu FC, Sharpe RM. 1987. Isolation of human Leydig cells which are highly responsive to human chorionic gonadotropin. J Clin Endocrinol Metab. 65(3):415–422. doi: 10.1210/jcem-65-3-415.
  • Singh KP, Kumari R, Pevey C, Jackson D, DuMond JW. 2009. Long duration exposure to cadmium leads to increased cell survival, decreased DNA repair capacity, and genomic instability in mouse testicular Leydig cells. Cancer Lett. 279(1):84–92. doi: 10.1016/j.canlet.2009.01.023.
  • Siu ER, Mruk DD, Porto CS, Cheng CY. 2009. Cadmium-induced testicular injury. Toxicol Appl Pharmacol. 238(3):240–249. doi: 10.1016/j.taap.2009.01.028.
  • Stohs SJ, Bagchi D. 1995. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med. 18(2):321–336. doi: 10.1016/0891-5849(94)00159-h.
  • Swiergosz-Kowalewska R. 2001. Cadmium distribution and toxicity in tissues of small rodents. Microsc Res Tech. 55(3):208–222.
  • Takiguchi M, Achanzar WE, Qu W, Li G, Waalkes MP. 2003. Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp Cell Res. 286(2):355–365. doi: 10.1016/s0014-4827(03)00062-4.
  • Togawa K, Le Cornet C, Feychting M, Tynes T, Pukkala E, Hansen J, Olsson A, Oksbjerg Dalton S, Nordby KC, Uuksulainen S, et al. 2016. Parental Occupational Exposure to Heavy Metals and Welding Fumes and Risk of Testicular Germ Cell Tumors in Offspring: A Registry-Based Case-Control Study. Cancer Epidemiol Biomarkers Prev. 25(10):1426–1434. doi: 10.1158/1055-9965.EPI-16-0328.
  • Trabert B, Chen J, Devesa SS, Bray F, McGlynn KA. 2015. International patterns and trends in testicular cancer incidence, overall and by histologic subtype, 1973-2007. Andrology. 3(1):4–12. doi: 10.1111/andr.293.
  • Turnbull C, Rahman N. 2011. Genome-wide association studies provide new insights into the genetic basis of testicular germ-cell tumour. Int J Androl. 34(4 Pt 2):e86-96–e97. discussion e96-87. doi: 10.1111/j.1365-2605.2011.01162.x.
  • Valko M, Morris H, Cronin MT. 2005. Metals, toxicity and oxidative stress. Curr Med Chem. 12(10):1161–1208. doi: 10.2174/0929867053764635.
  • Verhoeven RH, Louwman MW, Buntinx F, Botterweck AM, Lousbergh D, Faes C, Coebergh JW. 2011. Variation in cancer incidence in northeastern Belgium and southeastern Netherlands seems unrelated to cadmium emission of zinc smelters. Eur J Cancer Prev. 20(6):549–555. doi: 10.1097/CEJ.0b013e3283498e9c.
  • Verougstraete V, Lison D, Hotz P. 2002. A systematic review of cytogenetic studies conducted in human populations exposed to cadmium compounds. Mutat Res. 511(1):15–43. doi: 10.1016/s1383-5742(01)00070-9.
  • Vilahur N, Vahter M, Broberg K. 2015. The epigenetic effects of prenatal cadmium exposure. Curr Environ Health Rep. 2(2):195–203. doi: 10.1007/s40572-015-0049-9.
  • Virani S, Rentschler KM, Nishijo M, Ruangyuttikarn W, Swaddiwudhipong W, Basu N, Rozek LS. 2016. DNA methylation is differentially associated with environmental cadmium exposure based on sex and smoking status. Chemosphere. 145:284–290. doi: 10.1016/j.chemosphere.2015.10.123.
  • Waalkes MP. 1986. Effect of dietary zinc deficiency on the accumulation of cadmium and metallothionein in selected tissues of the rat. J Toxicol Environ Health. 18(2):301–313. doi: 10.1080/15287398609530870.
  • Waalkes MP, Anver M, Diwan BA. 1999a. Carcinogenic effects of cadmium in the noble (NBL/Cr) rat: induction of pituitary, testicular, and injection site tumors and intraepithelial proliferative lesions of the dorsolateral prostate. Toxicol Sci. 52(2):154–161. doi: 10.1093/toxsci/52.2.154.
  • Waalkes MP, Anver MR, Diwan BA. 1999b. Chronic toxic and carcinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes. J Toxicol Environ Health A. 58(4):199–214.
  • Waalkes MP, Chernoff SB, Klaassen CD. 1984a. Cadmium-binding proteins of rat testes. Apparent source of the protein of low molecular mass. Biochem J. 220(3):819–824. doi: 10.1042/bj2200819.
  • Waalkes MP, Chernoff SB, Klaassen CD. 1984b. Cadmium-binding proteins of rat testes. Characterization of a low-molecular-mass protein that lacks identity with metallothionein. Biochem J. 220(3):811–818. doi: 10.1042/bj2200811.
  • Waalkes MP, Kovatch R, Rehm S. 1991. Effect of chronic dietary zinc deficiency on cadmium toxicity and carcinogenesis in the male Wistar [Hsd: (WI)BR] rat. Toxicol Appl Pharmacol. 108(3):448–456. doi: 10.1016/0041-008x(91)90091-r.
  • Waalkes MP, Perantoni A. 1986. Isolation of a novel metal-binding protein from rat testes. Characterization and distinction from metallothionein. J Biol Chem. 261(28):13097–13103. doi: 10.1016/S0021-9258(18)69276-2.
  • Waalkes MP, Perantoni A. 1988. In vitro assessment of target cell specificity in cadmium carcinogenesis: interactions of cadmium and zinc with isolated interstitial cells of the rat testes. In Vitro Cell Dev Biol. 24(6):558–565. doi: 10.1007/BF02629091.
  • Waalkes MP, Perantoni A, Bhave MR, Rehm S. 1988. Strain dependence in mice of resistance and susceptibility to the testicular effects of cadmium: assessment of the role of testicular cadmium-binding proteins. Toxicol Appl Pharmacol. 93(1):47–61. doi: 10.1016/0041-008x(88)90024-5.
  • Waalkes MP, Poirier LA. 1984. In vitro cadmium-DNA interactions: cooperativity of cadmium binding and competitive antagonism by calcium, magnesium, and zinc. Toxicol Appl Pharmacol. 75(3):539–546. doi: 10.1016/0041-008x(84)90190-x.
  • Waalkes MP, Poirier LA. 1985. Interactions of cadmium with interstitial tissue of the rat testes. Uptake of cadmium by isolated interstitial cells. Biochem Pharmacol. 34(14):2513–2518. doi: 10.1016/0006-2952(85)90535-0.
  • Waalkes MP, Rehm S. 1992. Carcinogenicity of oral cadmium in the male Wistar (WF/NCr) rat: effect of chronic dietary zinc deficiency. Fundam Appl Toxicol. 19(4):512–520. doi: 10.1093/toxsci/19.4.512.
  • Waalkes MP, Rehm S, Cherian MG. 2000. Repeated cadmium exposures enhance the malignant progression of ensuing tumors in rats. Toxicol Sci. 54(1):110–120. doi: 10.1093/toxsci/54.1.110.
  • Waalkes MP, Rehm S, Devor DE. 1997. The effects of continuous testosterone exposure on spontaneous and cadmium-induced tumors in the male Fischer (F344/NCr) rat: loss of testicular response. Toxicol Appl Pharmacol. 142(1):40–46. doi: 10.1006/taap.1996.8005.
  • Waalkes MP, Rehm S, Riggs CW, Bare RM, Devor DE, Poirier LA, Wenk ML, Henneman JR. 1989. Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of effects of zinc on tumor induction in the prostate, in the testes, and at the injection site. Cancer Res. 49(15):4282–4288.
  • Waalkes MP, Rehm S, Riggs CW, Bare RM, Devor DE, Poirier LA, Wenk ML, Henneman JR, Balaschak MS. 1988. Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of tumor induction in the prostate and testes and at the injection site. Cancer Res. 48(16):4656–4663.
  • Waalkes MP, Rehm S, Sass B, Konishi N, Ward JM. 1991. Chronic carcinogenic and toxic effects of a single subcutaneous dose of cadmium in the male Fischer rat. Environ Res. 55(1):40–50. doi: 10.1016/s0013-9351(05)80139-2.
  • Wahba ZZ, Waalkes MP. 1990. Effect of in vivo low-dose cadmium pretreatment on the in vitro interactions of cadmium with isolated interstitial cells of the rat testes. Fundam Appl Toxicol. 15(4):641–650. doi: 10.1093/toxsci/15.4.641.
  • Wang B, Li Y, Shao C, Tan Y, Cai L. 2012. Cadmium and its epigenetic effects. Curr Med Chem. 19(16):2611–2620. doi: 10.2174/092986712800492913.
  • Wirth JJ, Mijal RS. 2010. Adverse effects of low level heavy metal exposure on male reproductive function. Syst Biol Reprod Med. 56(2):147–167. doi: 10.3109/19396360903582216.
  • Wuehler SE, Peerson JM, Brown KH. 2005. Use of national food balance data to estimate the adequacy of zinc in national food supplies: methodology and regional estimates. Public Health Nutr. 8(7):812–819. doi: 10.1079/phn2005724.
  • Xu LC, Sun H, Wang SY, Song L, Chang HC, Wang XR. 2005. The roles of metallothionein on cadmium-induced testes damages in Sprague-Dawley rats. Environ Toxicol Pharmacol. 20(1):83–87. doi: 10.1016/j.etap.2004.10.008.
  • Xu G, Zhou G, Jin T, Zhou T, Hammarstrom S, Bergh A, Nordberg G. 1999. Apoptosis and p53 gene expression in male reproductive tissues of cadmium exposed rats. Biometals. 12(2):131–139. doi: 10.1023/a:1009273711068.
  • Yamada T, Maita K, Nakamura J, Murakami M, Okuno Y, Hosokawa S, Matsuo M, Yamada H. 1994. Carcinogenicity studies of oxolinic acid in rats and mice. Food Chem Toxicol. 32(5):397–408. doi: 10.1016/0278-6915(94)90037-x.
  • Yamada T, Nakamura J, Murakami M, Okuno Y, Hosokawa S, Matsuo M, Yamada H. 1994. The correlation of serum luteinizing hormone levels with the induction of Leydig cell tumors in rats by oxolinic acid. Toxicol Appl Pharmacol. 129(1):146–154. doi: 10.1006/taap.1994.1238.
  • Yang MS, Lai KP, Cheng KY, Wong CK. 2000. Changes in endogenous Zn and Cu distribution in different cytosolic protein fractions in mouse liver after administration of a single sublethal dose of CdCl(2). Toxicology. 154(1-3):103–111. doi: 10.1016/s0300-483x(00)00320-6.
  • Zhou T, Jia X, Chapin RE, Maronpot RR, Harris MW, Liu J, Waalkes MP, Eddy EM. 2004. Cadmium at a non-toxic dose alters gene expression in mouse testes. Toxicol Lett. 154(3):191–200. doi: 10.1016/j.toxlet.2004.07.015.
  • Zhou T, Zhou G, Song W, Eguchi N, Lu W, Lundin E, Jin T, Nordberg G. 1999. Cadmium-induced apoptosis and changes in expression of p53, c-jun and MT-I genes in testes and ventral prostate of rats. Toxicology. 142(1):1–13. doi: 10.1016/s0300-483x(99)00115-8.
  • Zhu H, Li K, Liang J, Zhang J, Wu Q. 2011. Changes in the levels of DNA methylation in testis and liver of SD rats neonatally exposed to 5-aza-2′-deoxycytidine and cadmium. J Appl Toxicol. 31(5):484–495. doi: 10.1002/jat.1673.
  • Znaor A, Lortet-Tieulent J, Jemal A, Bray F. 2014. International variations and trends in testicular cancer incidence and mortality. Eur Urol. 65(6):1095–1106. doi: 10.1016/j.eururo.2013.11.004.

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