Antimutagenic activity of organosulfur compounds from Allium is associatedwith phase II enzyme induction

In a previous study, we showed that naturally occurring organosulfur compou nds (OSCs) from garlic and onion modulated the activation of carcino-en via the alteration of cytochromes P450. The present study was undertaken to de termine the incidence of the in vivo induction of phase II enzymes by indiv idual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS ), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1 mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on t he genotoxicity of carcinogens were evaluated with hepatic cytosols and mic rosomes from OSCs-treated rats. DADS strongly increased all the phase II en zymes activities examined, i.e. total glutathione S-transferase (GST) activ ity, mu GST activity, quinone reductase (QR) activity and epoxide hydrolase (EH) activity. In addition, DADS strongly increased the protein level of r GSTP1. QR activity, total and mu GST activities were also increased by DAS and DPDS whereas DPS increased only mu. GST activity and QR activity. To as sess the repercussions of these inductions on the genotoxicity of carcinoge ns, the effects of cytosols or microsomes from OSCs-treated rats on the mut agenicity of (+)-anti-7 beta ,8 alpha -dihydroxy-9 alpha ,10 alpha -oxy-7,8 ,9,10-tetrahydrobenzo[a]pyrene (BPDE), styrene oxide (SO) and 4-nitroquinol ine 1-oxide (4-NQO) were measured in the Ames test. DADS showed a very effe ctive antimutagenic activity against BPDE, SO and 4-NQO. DAS reduced the mu tagenicity of BPDE and SO. In contrast, DPS and DPDS showed little efficien t antimutagenic activity since they only reduced the mutagenicity of BPDE a nd 4-NQO, respectively. Interestingly, DADS appeared to be as effective as ethoxyquin, a model inducer of phase II enzymes, in both inducing phase II enzymes and inhibiting the mutagenicity of carcinogens. This study demonstr ated that the antimutagenic activities of OSCs against several ultimate car cinogens were closely related to their ability to induce phase II enzymes. (C) 2001 Elsevier Science B.V. All lights reserved.