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The effects of chemotherapy with bleomycin, etoposide, and cis‐platinum on telomeres in rat male germ cells
Author(s) -
Liu M.,
Maselli J.,
Hales B. F.,
Robaire B.
Publication year - 2015
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12102
Subject(s) - telomere , spermatid , etoposide , bleomycin , germ cell , biology , telomerase , andrology , germ cell tumors , dna damage , cisplatin , sperm , cancer research , chemotherapy , genetics , medicine , dna , gene
Summary Co‐administration of bleomycin, etoposide, and cis‐platinum ( BEP ) has increased the 5‐year survival rate of testis cancer patients to over 90%; however, this treatment induces chemotoxic effects on male germ cells. Treatment of male rats with BEP , using a similar schedule to that used in man, affects reproductive organ weights and sperm count, motility, and DNA integrity, as well as pup survival rates. Telomeres, specialized structures at the termini of chromosomes, play an important role in the maintenance of genetic stability. In previous studies, we demonstrated, using a spermatogonial cell line, that cis‐platinum and bleomycin damage telomeres and that cis‐platinum also inhibits telomerase activity. Our objective here was to test the hypothesis that in vivo exposure to the BEP regimen used to treat testis cancer targets telomeres in the male germ line. Adult male Brown Norway rats received chronic treatment with a BEP regimen. DNA double strand breaks were increased significantly in zygotene germ cells, as assessed by γ‐H2 AX immunofluorescence. Interestingly, treatment with this BEP regimen increased γ‐H2 AX foci in the telomere region of zygotene spermatocytes, but not in other germ cell types, such as pachytene cells, round spermatids, or elongating spermatids. Mean telomere lengths were reduced in zygotene, pachytene, round spermatid, elongating spermatid and cauda epididymal spermatozoa compared with the saline control group. Thus, telomere lengths did not recover during germ cell development. These studies demonstrate that BEP treatment is associated with an effect on telomeres.