Transformation Assay in Bhas 42 Cells: A Model Using Initiated Cells to Study Mechanisms of Carcinogenesis and Predict Carcinogenic Potential of Chemicals

REFERENCES

• Heidelberger C, Freeman AE, Pienta RJ, Sivak A, Bertram JS, Casto BC, et al. Cell transformation by chemical agents—a review and analysis of the literature. A report of the US Environmental Protection Agency Gene-Tox Program. Mutat Res. 1983;114:283–385.
   PubMed Web of Science ®Google Scholar
• IARC/NCI/EPA Working Group. Cellular and molecular mechanisms of cell transformation and standardization of transformation assays of established cell lines for the prediction of carcinogenic chemicals: overview and recommended protocols. Cancer Res. 1985;45:2395–2399.
   Web of Science ®Google Scholar
• Berwald Y, Sachs L. In vitro cell transformation with chemical carcinogens. Nature. 1963;200:1182–1184.
   PubMed Web of Science ®Google Scholar
• LeBoeuf RA, Kerckaert KA, Aardema MJ, Isfort RJ. Use of Syrian hamster embryo and BALB/c 3T3 cell transformation for assessing the carcinogenic potential of chemicals. In: McGregor DB, Rice JM, Venitt S (eds.), The Use of Short- and Medium-term Tests for Carcinogens and Data on Genetic Effects in Carcinogenic Hazard Evaluation (IARC Scientific Publications No 146). Lyon, France: International Agency for Research on Cancer; 1999:409–425.
   Google Scholar
• Mayorca G, Greenblatt M, Trauthen T, Soller A, Giordano R. Malignant transformation of BHK21 clone 13 cells in vitro by nitrosamines—a conditional state. Proc Natl Acad Sci USA. 1973;70:46–49.
   PubMed Web of Science ®Google Scholar
• O’Hayer KM, Counter CM. A genetically defined normal human somatic cell system to study ras oncogenesis in vivo and in vitro. Methods Enzymol. 2006;407:637–647.
   PubMed Web of Science ®Google Scholar
• Kakunaga T. A quantitative system for assay of malignant transformation by chemical carcinogens using a clone derived from BALB-3T3. Int J Cancer. 1973;12:463–473.
   PubMed Web of Science ®Google Scholar
• Kakunaga T, Crow JD. Cell variants showing differential susceptibility to ultraviolet light—induced transformation. Science. 1980;209:505–507.
   PubMed Web of Science ®Google Scholar
• DiPaolo JA, Takano K, Popescu NC. Quantitation of chemically induced neoplastic transformation of BALB-3T3 cloned cell lines. Cancer Res. 1972;32:2686–2895.
   PubMed Web of Science ®Google Scholar
• Boone CW. Malignant hemangioendotheliomas produced by subcutaneous inoculation of Balb/3T3 cells attached to glass beads. Science. 1975;188:68–70.
   PubMed Web of Science ®Google Scholar
• Newbold RF, Overell RW, Connell JR. Induction of immortality is an early event in malignant transformation of mammalian cells by carcinogens. Nature. 1982;299:633–635.
   PubMed Web of Science ®Google Scholar
• Berwald Y, Sachs L. In vitro transformation of normal cells to tumor cells by carcinogenic hydrocarbons. J Natl Cancer Inst. 1965;35:641–661.
   PubMed Web of Science ®Google Scholar
• Yamada Y, Mori H. Multistep carcinogenesis of the colon in Apc(Min/+) mouse. Cancer Sci. 2007;98:6–10.
   PubMed Web of Science ®Google Scholar
• Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–767.
   PubMed Web of Science ®Google Scholar
• Hemminki K, Mutanen P. Genetic epidemiology of multistage carcinogenesis. Mutat Res. 2001;473:11–21.
   PubMed Web of Science ®Google Scholar
• Land H, Parada LF, Weinberg RA. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983;304:596–602.
   PubMed Web of Science ®Google Scholar
• Ruley HE. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983;304:602–606.
   PubMed Web of Science ®Google Scholar
• Newbold RF, Overell RW. Fibroblast immortality is a prerequisite for transformation by EJ c-Ha-ras oncogene. Nature. 1983;304:648–651.
   PubMed Web of Science ®Google Scholar
• Boutwell RK. Some biological aspects of skin carcinogenesis. Prog Exp Tumor Res. 1964;4:207–250.
   PubMed Web of Science ®Google Scholar
• Singh RP, Agarwal R. SENCAR mouse skin tumorigenesis model. In: Teicher BA (ed.), Tumor Models in Cancer Research. Totowa, NJ: Humana Press; 2002:359–380.
   Google Scholar
• Zarbl H, Sukumar S, Arthur AV, Martin-Zanca D, Barbacid M. Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature. 1985;315:382–385.
   PubMed Web of Science ®Google Scholar
• Müller R, Bravo R, Burckhardt J, Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984;312:716–720.
   PubMed Web of Science ®Google Scholar
• Sasaki K, Mizusawa H, Ishidate M. Isolation and characterization of ras-transfected BALB/3T3 clone showing morphological transformation by 12-O-tetradecanoyl-phorbol-13-acetate. Jpn J Cancer Res. 1988;79:921–930.
   PubMedGoogle Scholar
• Shih C, Shilo BZ, Goldfarb MP, Dannenberg A, Weinberg RA. Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. Proc Natl Acad Sci USA. 1979;76:5714–5718.
   PubMed Web of Science ®Google Scholar
• Tabin CJ, Bradley SM, Bargmann CI, Weinberg RA, Papageorge AG, Scolnick EM, Dhar R, Lowy DR, Chang EH. Mechanism of activation of a human oncogene. Nature. 1982;300:143–149.
   PubMed Web of Science ®Google Scholar
• Reddy EP, Reynolds RK, Santos E, Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature. 1982;300:149–152.
   PubMed Web of Science ®Google Scholar
• Taparowsky E, Suard Y, Fasano O, Shimizu K, Goldfarb M, Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982;300:762–765.
   PubMed Web of Science ®Google Scholar
• Wigler M, Sweet R, Sim GK, Wold B, Pellicer A, Lacy E, Maniatis T, Silverstein S, Axel R. Transformation of mammalian cells with genes from procaryotes and eucaryotes. Cell. 1979;16:777–785.
   PubMed Web of Science ®Google Scholar
• Southern PJ, Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1:327–341.
   PubMedGoogle Scholar
• Denayer E, de Ravel T, Legius E. Clinical and molecular aspects of RAS related disorders. J Med Genet. 2008;45:695–703.
   PubMed Web of Science ®Google Scholar
• Sueoka E, Sueoka N, Okabe S, Komori A, Suganuma M, Kozu T, Fujiki H. Tumourigenicity of MTG8, a leukaemia-related gene, in concert with v-Ha-ras gene in BALB/3T3 cells. Br J Haematol. 1998;101:737–742.
   PubMed Web of Science ®Google Scholar
• Suganuma M, Kurusu M, Okabe S, Sueoka N, Yoshida M, Wakatsuki Y, Fujiki H. Helicobacter pylori membrane protein 1: a new carcinogenic factor of Helicobacter pylori. Cancer Res. 2001;61:6356–6359.
   PubMed Web of Science ®Google Scholar
• Peterson AR, Mondal S, Brankow DW, Thon W, Heidelberger C. Effects of promoters on DNA synthesis in C3H/10T1/2 mouse fibroblasts. Cancer Res. 1977;37:3223–3227.
   PubMed Web of Science ®Google Scholar
• Frantz CN, Stiles CD, Scher CD. The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate enhances the proliferative response of Balb/c-3T3 cells to hormonal growth factors. J Cell Physiol. 1979;100:413–424.
   PubMed Web of Science ®Google Scholar
• Komori A, Yatsunami J, Suganuma M, Okabe S, Abe S, Sakai A, Sasaki K, Fujiki H. Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation. Cancer Res. 1993;53:1982–1985.
   PubMed Web of Science ®Google Scholar
• Kawashima H, Ogose A, Hotta T, Ito T, Endo N, Tamura K, Nakano K. Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated Ras mutation. J Exp Clin Cancer Res. 2005;24:617–624.
   PubMed Web of Science ®Google Scholar
• Sasaki K, Mizusawa H, Ishidate M, Tanaka N. Establishment of a highly reproducible transformation assay of a ras-transfected BALB 3T3 clone by treatment with promoters. In: Kuroda Y, Shankel DM, Waters MD (eds.), Antimutagenesis and Anticarcinogenesis Mechanisms II (Basic Life Sciences Vol. 52). New York: Plenum Publishing;1990:411–416.
   Google Scholar
• Sasaki K, Mizusawa H, Ishidate M, Tanaka N. Transformation of ras transfected BALB 3T3 clone (Bhas 42) by promoters: application for screening and specificity of promoters. Toxicol In Vitro. 1990;4:657–659.
   PubMed Web of Science ®Google Scholar
• Kakunaga T. Requirement for cell replication in the fixation and expression of the transformed state in mouse cells treated with 4-nitroquinoline-1-oxide. Int J Cancer. 1974;14:736–742.
   PubMed Web of Science ®Google Scholar
• Sakamoto Y, Takeda Y, Takagi H, Tsuchiya T, Shoji A, Miyazaki K, Umeda M. Inhibition of focus formation of transformed cloned cells by contact with non-transformed BALB/c 3T3 A31-1-1 cells. Cancer Lett. 1999;136:159–165.
   PubMed Web of Science ®Google Scholar
• Katoh F, Klein JL, Bignami M, Yamasaki H. Association of viral oncogene-induced changes in gap junctional intercellular communication and morphological transformation in BALB/c3T3 cells. Carcinogenesis. 1993;14:435–440.
   PubMed Web of Science ®Google Scholar
• Ohmori K, Sasaki K, Asada S, Tanaka N, Umeda M. An assay method for the prediction of tumor promoting potential of chemicals by the use of Bhas 42 cells. Mutat Res. 2004;557:191–202.
   PubMed Web of Science ®Google Scholar
• Asada S, Sasaki K, Tanaka N, Takeda K, Hayashi M, Umeda M. Detection of initiating as well as promoting activity of chemicals by a novel cell transformation assay using v-Ha-ras-transfected BALB/c 3T3 cells (Bhas 42 cells). Mutat Res. 2005;588:7–21.
   PubMed Web of Science ®Google Scholar
• Suganuma M, Kurusu M, Suzuki K, Nishizono A, Murakami K, Fujioka T, Fujiki H. New tumor necrosis factor-α-inducing protein released from Helicobacter pylori for gastric cancer progression. J Cancer Res Clin Oncol. 2005;131:305–313.
   PubMed Web of Science ®Google Scholar
• Suganuma M, Okabe S, Marino MW, Sakai A, Sueoka E, Fujiki H. Essential role of tumor necrosis factor α (TNF-α) in tumor promotion as revealed by TNF- α-deficient mice. Cancer Res. 1999;59:4516–4518.
   PubMed Web of Science ®Google Scholar
• Fujiki H, Takeuchi H, Nishitani N, Yamanaka H, Suzuki K, Kurusu M, Suganuma M. Carcinogenic potential of tobacco tar-resistant Staphylococcus aureus in buccal cavity. J Cancer Res Clin Oncol. 2004;130:301–305.
   PubMed Web of Science ®Google Scholar
• Sasaki K, Bohnenberger S, Hayashi K, Kunkelmann T, Muramatsu D, Poth A, et al. Photo catalogue for the classification of foci in the BALB/c 3T3 cell transformation assay. Mutat Res. 2012;744:42–53.
   PubMed Web of Science ®Google Scholar
• Ohmori K, Umeda M, Tanaka N, Takagi H, Yoshimura I, Sasaki K, et al. An inter-laboratory collaborative study by the Non-Genotoxic Carcinogen Study Group in Japan, on a cell transformation assay for tumour promoters using Bhas 42 cells. Altern Lab Anim. 2005;33:619–639.
   PubMed Web of Science ®Google Scholar
• Arai S, Tanaka N, Sasaki K, Sakai A. A study on the dose setting of test chemicals for the promotion assay in Bhas 42 cell transformation assay. AATEX. 2010;15:6–13.
   Google Scholar
• Mondal S, Brankow DW, Heidelberger C. Two-stage chemical oncogenesis in cultures of C3H/10T1/2 cells. Cancer Res. 1976;36:2254–2260.
   PubMed Web of Science ®Google Scholar
• Sakai A, Sato M. Improvement of carcinogen identification in BALB/3T3 cell transformation by application of a 2-stage method. Mutat Res. 1989;214:285–296.
   PubMed Web of Science ®Google Scholar
• Tsuchiya T, Umeda M. Relationship between exposure to TPA and appearance of transformed cells in MNNG-initiated transformation of BALB/c 3T3 cells. Int J Cancer. 1997;73:271–276.
   PubMed Web of Science ®Google Scholar
• Enomoto T, Yamasaki H. Phorbol ester-mediated inhibition of intercellular communication in BALB/c 3T3 cells: relationship to enhancement of cell transformation. Cancer Res. 1985;45:2681–2688.
   PubMed Web of Science ®Google Scholar
• Umeda M. Detection of non-genotoxic carcinogens using ras-transfected Bhas 42 cells. ALTEX. 2006; 23 Special Issue:450–455.
   Google Scholar
• Ohmori K. In vitro assays for the prediction of tumorigenic potential of non-genotoxic carcinogens. J Health Sci. 2009;55:20–30.
   Web of Science ®Google Scholar
• Muramatsu D, Sasaki K, Kuroda S, Hayashi K, Tanaka N, Sakai A. Comparison of sensitivity to arsenic compounds between a Bhas 42 cell transformation assay and a BALB/c 3T3 cell transformation assay. Mutat Res. 2009;675:66–70.
   PubMed Web of Science ®Google Scholar
• Sakai A. BALB/c 3T3 cell transformation assays for the assessment of chemical carcinogenicity. AATEX. 2008;14(Special Issue):367–373.
   Google Scholar
• Benigni R, Bossa C, Tcheremenskaia O. In vitro cell transformation assays for an integrated, alternative assessment of carcinogenicity: a data-based analysis. Mutagenesis. 2013;28:107–116.
   PubMed Web of Science ®Google Scholar
• Arai S, Sakai A, Hayashi K, Sasaki K, Muramatsu D, Endou N, Umeda M, Tanaka N. A high-throughput cell transformation assay applicable to automation for detecting potential chemical carcinogens using Bhas 42 cells. AATEX. 2013;18:1–19.
   Google Scholar
• Sakai A, Sasaki K, Muramatsu D, Arai S, Endou N, Kuroda S, et al. A Bhas 42 cell transformation assay on 98 chemicals: the characteristics and performance for the prediction of chemical carcinogenicity. Mutat Res. 2010;702:100–122.
   PubMed Web of Science ®Google Scholar
• Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology. OECD Series on Testing and Assessment, Number 31: Detailed Review Paper on Cell Transformation Assays for Detection of Chemical Carcinogens. ENV/JM/MONO(2007) 18. Paris: Organisation for Economic Co-operation and Development; 2007.
   Google Scholar
• Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology. 1998;139:4252–4263.
   PubMed Web of Science ®Google Scholar
• Schechtman LM, Stokes WS. The FDA's regulatory role in the ICCVAM process. Altern Lab Anim. 2004;32(Suppl 1B):663–668.
   PubMed Web of Science ®Google Scholar
• Tanaka N, Sasaki K, Hayashi K, Sakai A, Asada S, Muramatsu D, et al. An interlaboratory collaborative study on a cell transformation assay using Bhas 42 cells. AATEX. 2009;14:831–848.
   Google Scholar
• Sakai A, Sasaki K, Hayashi K, Muramatsu D, Arai S, Endou N, et al. An international validation study of a Bhas 42 cell transformation assay for the prediction of chemical carcinogenicity. Mutat Res. 2011;725:57–77.
   PubMed Web of Science ®Google Scholar
• Hayashi M, Kojima H, Corvi R, Stokes W, Jacobs A, Morita T, Schechtman L. Suzuki M. Bhas 42 Cell Transformation Assay Validation Study Report. Paris: Organisation for Economic Co-operation and Development; 2012.
   Google Scholar
• IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. http://monographs.iarc.fr/.
   Google Scholar
• Chemical Carcinogenesis Research Information System. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?. CCRIS.
   Google Scholar
• Sasaki K, Muramatsu D, Arai S, Endou N, Sakai A, Umeda M, Tanaka N. A spectrophotometric quantitative transformation assay using a cell viability chromogenic reagent followed by selective killing of normal contact-inhibited cells with hydrogen peroxide in Bhas 42 cells. (In preparation.)
   Google Scholar
• The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013;499:43–49.
   PubMedGoogle Scholar
• The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507:315–322.
   PubMed Web of Science ®Google Scholar
• Shimizu K, Goldfarb M, Suard Y, Perucho M, Li Y, Kamata T, Feramisco J, Stavnezer E, Fogh J, Wigler MH. Three human transforming genes are related to the viral ras oncogenes. Proc Natl Acad Sci USA. 1983;80:2112–2116.
   PubMed Web of Science ®Google Scholar
• Cooper CS. The role of non-ras transforming genes in chemical carcinogenesis. Environ Health Perspect. 1991;93:33–40.
   PubMed Web of Science ®Google Scholar
• Hsiao WL, Gattoni-Celli S, Weinstein IB. Oncogene-induced transformation of C3H 10T1/2 cells is enhanced by tumor promoters. Science. 1984;226:552–555.
   PubMed Web of Science ®Google Scholar
• Dotto GP, Parada LF, Weinberg RA. Specific growth response of ras-transformed embryo fibroblasts to tumour promoters. Nature. 1985;318:472–475.
   PubMed Web of Science ®Google Scholar
• Hsiao WL, Wu T, Weinstein IB. Oncogene-induced transformation of a rat embryo fibroblast cell line is enhanced by tumor promoters. Mol Cell Biol. 1986;6:1943–1950.
   PubMed Web of Science ®Google Scholar
• Kowalski LA, Laitinen AM, Mortazavi-Asl B, Wee RK, Erb HE, Assi KP, Madden Z. In vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus DNA-carrying C3H/10T(1/2) cell line. Environ Mol Mutagen. 2000;35:300–311.
   PubMed Web of Science ®Google Scholar
• Kowalski LA, Assi KP, Wee RK, Madden Z. In vitro prediction of carcinogenicity using a bovine papillomavirus DNA–carrying C3H/10T 1/2 cell line (T1). II: Results from the testing of 100 chemicals. Environ Mol Mutagen. 2001;37:231–240.
   PubMed Web of Science ®Google Scholar
• Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997;88:593–602.
   PubMed Web of Science ®Google Scholar
• Collado M, Serrano M. Senescence in tumours: evidence from mice and humans. Nat Rev Cancer. 2010;10:51–57.
   PubMed Web of Science ®Google Scholar
• Nakajima D, Asada S, Kageyama S, Yamamoto T, Kuramochi H, Tanaka N, Takeda K, Goto S. Activity related to the carcinogenicity of plastic additives in the benzophenone group. J UOEH. 2006;28:143–156.
   PubMedGoogle Scholar
• Goto S, Asada S, Fushiwaki Y, Mori Y, Tanaka N, Umeda M, Nakajima D, Takeda K. Tumor-promoting activity and mutagenicity of 5 termiticide compounds. J UOEH. 2004;26:423–430.
   PubMedGoogle Scholar
• Ohmori K, Kawamura Y. Cell transformation activities of abietic acid and dehydroabietic acid: safety assessment of possible contaminants in paper and paperboard for food contact use. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2009;26:568–573.
   PubMed Web of Science ®Google Scholar
• Sakai A, Suzuki C, Masui Y, Kuramashi A, Takatori K, Tanaka N. The activities of mycotoxins derived from Fusarium and related substances in a short-term transformation assay using v-Ha-ras-transfected BALB/3T3 cells (Bhas 42 cells). Mutat Res. 2007;630:103–111.
   PubMed Web of Science ®Google Scholar
• Ezoe Y, Ohkubo T, Ohmori K, Fushiwaki Y, Mori Y, Umeda M, Goto S. Promoter and mutagenic activity of particulate matter collected from urban air. J Health Sci. 2004;50:181–184.
   Web of Science ®Google Scholar
• Ohmori K, Sato Y, Nakajima D, Kageyama S, Shiraishi F, Fujimaki T, Goto S. Characteristics of the transformation frequency at the tumor promotion stage of airborne particulate and gaseous matter at ten sites in Japan. Environ Sci Process Impacts. 2013;15:1031–1040.
   Google Scholar
• Hasegawa G, Shimonaka M, Ishihara Y. Differential genotoxicity of chemical properties and particle size of rare metal and metal oxide nanoparticles. J Appl Toxicol. 2012;32:72–80.
   PubMed Web of Science ®Google Scholar
• Weisensee D, Poth A, Roemer E, Conroy LL, Schlage WK. Cigarette smoke-induced morphological transformation of Bhas 42 cells in vitro. Altern Lab Anim. 2013;41:181–189.
   PubMed Web of Science ®Google Scholar