Diallyl sulfide (DAS*), a major flavour and fragrance component of garlic oil (1), has been shown to be an effective inhibitor of tumorigenesis by diverse metabolically activated chemical carcinogens <2-5). In the most striking example of chemoprevention, Wargovich and co-workers reported (4) that pretreatment with DAS completely prevented the formation in rat oesophagus of both malignant and premalignant lesions by /V-nitrosomethylbenzylamine (NMBzA), an exceptionally potent and selective oesophageal carcinogen in this species (6). After preadministration of DAS, a significant reduction has been observed in nuclear aberrations induced by NMBzA and dimethylhydrazine (4,7) but not in the nucleotoxicity of the direct-acting methylating•Abbreviations: DAS, diallyl sulfide; NMBzA, N-nitrosomethylbenzylamine; O^-MEdG, C^-methyldeoxyguanosine, 7-MEdG, 7-methyldeoxyguanosine.© Oxford University Press carcinogens /V-nitrosomethylurea and /V-methyl-/V'-nitro-/Vnitrosoguanidine (7). Studies in vitro have shown that DAS also is an inhibitor of oxidative metabolism by cytochrome P450 enzymes of a number of carcinogenic nitrosamines, including NMBzA, /V-nitrosodimethylamine, /V-nitrosodiethylamine and 4-(A'-memyl-A^-nirjosarnino)-l-(3-pyridyl)-l-butanone (4,(8)(9)(10). These findings suggested that DAS may block nitrosamineinduced tumorigenesis by inhibiting nitrosamine bioactivation in situ. In the present investigation, we have examined this possibility by assessing the effects of DAS on the overall metabolism of NMBzA and on DNA methylation by NMBzA in vivo.In the protocol developed by Wargovich and co-workers (4), rats received five weekly treatments consisting of an i.g. dose of 200 mg/kg of DAS followed 3 h later by a s.c. injection of 3.5 mg/kg of NMBzA. However, in vitro demethylation of NMBzA was significantly lower by hepatic microsomes prepared 18 h after a similar dose of DAS than by microsomes collected 3 h post-treatment (8). In order to determine whether there is a similar difference in vivo between immediate and delayed effects of DAS on overall NMBzA metabolism, we monitored the formation of 14 CO 2 and radioactive urinary metabolites from [methyll4

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