[Modulation of mutagenic drug-induced unscheduled DNA synthesis (UDS) in primary rat hepatocytes by diallyl trisulfide].
Most anticancer drugs are mutagenic/carcinogenic. A possible exception is diallyl trisulfide (DAT), a component of garlic, which inhibits growth of transplantable tumors in vitro and in vivo and mutagenicity and carcinogenicity of genotoxic agents. It is an antimutagenic anticancer chemical. Its modulating effect on induction of UDS by mutagenic mitomycin C (MMC), cyclophosphamide (CP), and cis-diamine dichloroplatin (DDP) was investigated with the assay in primary cultures of Wistar rat hepatocytes by autoradiographic technique. Results showed that MMC (1-10 mumol/L), CP (0.316-3.16mmol/L), and DDP(3.16-31.6mumol/L) resulted in a significant induction of dose-dependent UDS and that DAT (0.5-4.0 mumol/L) significantly enhanced induction of UDS by MMC, CP and DDP while DAT itself did not. A dose-response relation was also observed between the dosage of DAT and the enhancement of induction of UDS. Hepatocellular enzymes for metabolic activation of indirect mutagens may not be involved in the enhancement of UDS-induction since DAT also increased UDS level induced by direct mutagen DDP. DAT promotes UDS induction probably by increasing repair of damaged 4-DNA. DAT, an anti-infection antibiotic, may be used in cancer chemotherapy to alleviate the adverse side effects of chemotherapeutic agents with mutagenic/carcinogenic activities.
Deng
D J
DJ
Beijing Institute for Cancer Research.
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D008099:Liver / Q000166:cytology*; D008297:Male; D016685:Mitomycin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D013440:Sulfides; C042577:diallyl trisulfide; D016685:Mitomycin; D003520:Cyclophosphamide; D004247:DNA; D002945:Cisplatin