Antimutagenic activity of organosulfur compounds from Allium is associated with phase II enzyme induction.
In a previous study, we showed that naturally occurring organosulfur compounds (OSCs) from garlic and onion modulated the activation of carcinogen via the alteration of cytochromes P450. The present study was undertaken to determine the incidence of the in vivo induction of phase II enzymes by individual OSCs on the genotoxicity of several carcinogens. Diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), were administered by gavage (1mmol/kg) to male SPF Wistar rats for 4 consecutive days. The effects of treatments on phase II enzymes and on the genotoxicity of carcinogens were evaluated with hepatic cytosols and microsomes from OSCs-treated rats. DADS strongly increased all the phase II enzymes activities examined, i.e. total glutathione S-transferase (GST) activity, mu GST activity, quinone reductase (QR) activity and epoxide hydrolase (EH) activity. In addition, DADS strongly increased the protein level of rGSTP1. 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 assess the repercussions of these inductions on the genotoxicity of carcinogens, the effects of cytosols or microsomes from OSCs-treated rats on the mutagenicity of (+)-anti-7beta,8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), styrene oxide (SO) and 4-nitroquinoline 1-oxide (4-NQO) were measured in the Ames test. DADS showed a very effective antimutagenic activity against BPDE, SO and 4-NQO. DAS reduced the mutagenicity of BPDE and SO. In contrast, DPS and DPDS showed little efficient antimutagenic activity since they only reduced the mutagenicity of BPDE and 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 demonstrated that the antimutagenic activities of OSCs against several ultimate carcinogens were closely related to their ability to induce phase II enzymes.
Guyonnet
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Institut National de la Recherche Agronomique, Unité Mixte de Recherche de Toxicologie Alimentaire, BP 86510, 17 rue Sully, 21065 Dijon Cedex, France.
Belloir
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Suschetet
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Siess
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Le Bon
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D000284:Administration, Oral; D000490:Allium; D000498:Allyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016587:Antimutagenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004220:Disulfides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects*; D004851:Epoxide Hydrolases / Q000096:biosynthesis; D005982:Glutathione Transferase / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D011407:Propane / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D013440:Sulfides / Q000494:pharmacology
D000498:Allyl Compounds; D016587:Antimutagenic Agents; D004220:Disulfides; D009153:Mutagens; D013440:Sulfides; C028009:diallyl disulfide; C038491:allyl sulfide; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C041288:n-propyl disulfide; C087894:dipropyl sulfide; D011407:Propane