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

Abstract

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.

Human sulphotransferases are involved in the activation of aristolochic acids and are expressed in renal target tissue

“…Using the 32 P‐post‐labelling technique, Schmeiser et al 3 detected aristolochic acid‐specific DNA adducts in renal and urothelial tissue from patients suffering from Chinese herb nephropathy up to 27 months after termination of the treatment. Aristolochic acids showed strong carcinogenic activity in rats, mice and rabbits; kidney and ureter were major target tissues 4, 5, 6, 7, 8, 9…”

Effect of Diclofenac and Naproxen on Drug-Metabolizing Enzymes in Mice.

“…Therefore, any agent that could inhibit or block the activities of enzymes responsible for the biotransformation of a particular procarcinogen to its carcinogenic form is likely to act as a chemopreventers provided it by itself does not possess any toxic and/ or carcinogenic properties. Some of agents that act in this way are dithiocarbamates [1], isothiocyanates [18], and diallylsulfide [19]. The consequent increase in GST might stimulate the detoxification of carcinogenic metabolites with reduced glutathione used as a cofactor.…”

Effects of compounds of plant origin on the mutagenicity and metabolism of the tobacco‐specific nitrosamine NNK

“…In this study, we report the effects of five phytochemicals on the bioactivation-dependent rnutagenesis P nd metabolism of the tobacco-specific nitrosarnine NNK. The metabolism of NNK involves several pathways that tumours in laboratory rodents (Wargovich, 1987;Wargovich et al, 1988;Sparnins et al, 1988;Hadjiolov et al ,1993). These effects have been associated with the inhibition of microsomal monooxygenase activity and/ or enhanced glutathione-S-transferase activity (Sparnins er al., 1988;Brady et al, 1988;Maurya and Singh, 1991;Ludeke et al, 1992).…”