Effect of diallyl sulfide on aristolochic acid-induced forestomach carcinogenesis in rats

In this study the development of aristolochic acid (AA) induced tumors in rats with and without diallyl sulfide (DAS) was studied. Experiments were also conducted to establish the effects of DAS administration on AA-derived DNA single-stranded regions and DNA adduct formation in the forestomach of such animals. Forestomach, urinary bladder and thymus tumors were induced in male BD-6 rats after oral treatment for 12 weeks with AA (2 x 10 mg/kg/week). Administration of 150 mg/kg DAS intragastrically 4 h prior to AA treatment reduced significantly the number of rats that developed forestomach tumors (6-9 months after the start of experiment). The incidence of AA-induced forestomach tumors was 10% (two out of 20 rats) after co-administration of DAS and 60% (12 out of 20 animals) when AA was administered alone. The high dose of DAS (2 x 150 mg/kg) markedly inhibited the formation of squamous cell carcinomas in the forestomach. However, the thioether did not prevent the formation of forestomach and urinary bladder papillomatosis. Additionally, DAS co-administration decreased the accumulation of single-stranded regions in rat forestomach DNA. Using the nuclease P1 enhancement method of the 32P-postlabeling assay, a decrease in the level of AA-derived adducts was also detected after co-administration of DAS. We conclude that the decrease of DNA damage after DAS co-administration is associated with the delay in conversion of papillomas to malignant forestomach tumors.