- Publication date : 2013-03-04
Delbès G, Chan D, Hales BF, Trasler JM, Robaire B. Selective induction of glutathione S-transferases in round spermatids from the Brown-Norway rat by the chemotherapeutic regimen for testicular cancer. Reprod. Toxicol. 2013;36:24-32. doi: 10.1016/j.reprotox.2012.10.012. PubMed PMID: 23200778.
aldehyde dehydrogenase animals antineoplastic combined chemotherapy protocols bleomycin blotting, western cisplatin dna methylation enzyme induction epigenesis, genetic etoposide glutathione transferase isoenzymes male metabolic detoxication, phase i metabolic detoxication, phase ii promoter regions, genetic rats rats, inbred bn real-time polymerase chain reaction reverse transcriptase polymerase chain reaction spermatids testicular neoplasms
Chemotherapeutic drugs can affect DNA in male germ cells, thereby impacting on the integrity of the genome transmitted to offspring. Drug metabolizing enzymes can protect cells from xenobiotic insult. We analyzed the expression pattern of such enzymes in isolated round spermatids from rats exposed to drugs used to treat testicular cancer: bleomycin, etoposide, and cisplatin (BEP). The number of isozymes expressed and the overall relative expression values were highest for the glutathione S-transferases (GSTs). Moreover, BEP treatment significantly increased the expression of 8 GSTs and 3 aldehyde dehydrogenases. Increased expression of GST isozymes was confirmed by qRT-PCR and Western blot analysis. Although Gst genes can be targets for epigenetic modifications, promoter DNA methylation was not affected by BEP treatment. As GSTs are involved in drug resistance mechanisms, we hypothesize that BEP induction of GST expression may lead to the survival of damaged germ cells and the production of abnormal sperm.