Vitamin C Modulation of Cisplatin-Induced Cytogenotoxicity in Bone Marrow, Spermatogonia and its Transmission in the Male Germline of Swiss Mice

Abstract

Relative modulatory effects of three different doses of vitamin C (VC), 10, 20 and 40 mg/kg, on cytogenotoxicity induced by cisplatin (CP) 5 mg/kg were assessed from the comparison of chromosomal aberrations (CAs) and mitotic index in bone marrow cells, micronucleus test (MNT) in polychromatic erythrocytes from the somatic cell line and spermatogonial chromosome aberrations (SCAs), primary spermatocytic chromosome analysis and sperm morphology assay from the male germline of VC-pretreated and CP-alone treated mice.

Each pretreatment dose of VC protected bone marrow cells from the CP-induced cytogenotoxicity by decreasing the aberrant metaphases, CAs and MN significantly, particularly the lower doses. The protection was inversely proportional to the pretreated dose of VC i.e., the higher the dose of VC the less protection was provided. The lower doses of VC also protected the spermatogonial cells by significantly decreasing the CP-induced aberrant metaphases and SCAs, whereas the highest dose potentiated such effects by increasing them significantly. Besides, transmission of CP-induced cytogenotoxicity in the male germline was enhanced significantly in all VC pretreated mice, resulting in an increase in the frequency of aberrant primary spermatocytes and abnormal sperm. Since the spermatogonial cells with gross effects were eliminated/died, the tolerable effects stabilized in some of them were transmitted through the male germline with the consequent increase in the manifestation of aberrant primary spermatocytes and abnormal sperm. However, VC failed to decrease in the transmission of such effects.

Thus, the protective action of VC was dose dependent and tissue specific. Moreover, the time of VC treatment i.e., its pre- or post-treatment to the exposure of cells to cytogenotoxic substances is important in providing protection from or potentiation of the cytogenotoxic effects.

Keywords:

• Vitamin C modulation
• cisplatin
• cytogenotoxicity
• chromosomal aberration
• mitotic index
• micronucleus
• spermatogonia
• primary spermatocyte
• Swiss mice