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Apoptotic response of spermatogenic cells to the germ cell mutagens etoposide, adriamycin, and diepoxybutane
Author(s) -
Sjöblom Tiina,
West Anne,
Lähdetie Jaana
Publication year - 1998
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/(sici)1098-2280(1998)31:2<133::aid-em5>3.0.co;2-n
Subject(s) - apoptosis , etoposide , germ cell , biology , spermatogenesis , cell cycle , mutagen , microbiology and biotechnology , cancer research , andrology , carcinogen , genetics , gene , endocrinology , chemotherapy , medicine
In testis, apoptosis is a way to eliminate damaged germ cells during their development. In this study, we evaluated the ability of three germ cell mutagens to induce apoptosis (or programmed cell death) at specific stages of rat seminiferous epithelial cycle. These chemicals include the cancer chemotherapy drugs etoposide and adriamycin and the butadiene metabolite diepoxybutane. According to our results, etoposide is a very potent inducer of apoptosis in male rat germ cells and the cell types most sensitive to it include all types of spermatogonia, zygotene, and early pachytene spermatocytes and meiotically dividing spermatocytes. Also, adriamycin causes an increase in apoptosis at specific stages of seminiferous epithelial cycle and the most sensitive cell types are type A 3–4 spermatogonia, preleptotene, zygotene, and early pachytene spermatocytes. Die poxybutane does not cause any significant increase in the frequency of apoptosis in rat testis. In addition, we studied whether p53 is taking part in the apoptotic response of spermatogenic cells by studying the levels of p53 protein in testis before and after chemical treatment. No accumulation of p53 in testis was seen after treatment with these three chemicals. The expression of two p53‐regulated genes, p21 WAF1 and mdm 2, was also studied but no increase in the levels of mRNA of these genes was observed after treatment. The results indicate that apoptosis should be taken into consideration when the genotoxic effects of chemicals are evaluated in germ cells. Environ. Mol. Mutagen. 31:133–148, 1998 © 1998 Wiley‐Liss, Inc.