title: Selective induction of glutathione S-transferases in round spermatids from the Brown-Norway rat by the chemotherapeutic regimen for testicular cancer.
abstract: 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.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Delbès
authors.forename: Donovan
authors.initials: D
authors.lastname: Chan
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Hales
authors.forename: Jacquetta M
authors.initials: JM
authors.lastname: Trasler
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaire
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D019175:DNA Methylation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005047:Etoposide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013087:Spermatids / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D001761:Bleomycin; D005047:Etoposide; D000444:Aldehyde Dehydrogenase; D005982:Glutathione Transferase; D002945:Cisplatin