Inhibition by allyl sulfides and crushed garlic of O6-methylguanine formation in liver DNA of dimethylnitrosamine-treated rats

Garlic consumption is linked with lower incidences of certain cancers perhaps because garlic-derived allyl sulfides inhibit nitrosamine activation by cytochrome P450s. To help evaluate this view, effects of allyl sulfides on O-6-methylguanine (O(6)MG) levels were examined in liver of rats injected with 20 mg/kg of liver carcinogen dimethylnitrosamine (DMN) and killed 3 h later DNA was isolated and hydrolyzed, and O(6)MG/guanine ratios were determined by HPLC-fluorescence. Mean inhibition of O(6)MG formation fell from 89% for 200 to 33% for 12 mg diallyl sulfide (DAS) per kilogram gavaged 18 h before DMN injection. Gavage of DAS 3 or 6 h (instead of 18 h) before DMN injection significantly reduced inhibitions. Mean inhibitions for diallyl disulfide, diallyl sulfoxide, and diallyl sulfone (75-100 mg/kg) gavaged 18 h before DMN were 39%, 72%, and 82%. In lung and kidney, DAS produced mean inhibitions of 98% and 74% compared with 89% in liver When methylnitrosourea was injected instead of DMN, neither DAS nor DADS inhibited O(6)MG formation in liver DNA. Feeding 2.5% garlic for 7 days inhibited DMN-induced O(6)MG formation in liver DNA by 46%, similar to that expected from the estimated yield of allyl sulfides from garlic. Hence, dosing with DAS or feeding garlic may be useful chemopreventive strategies against nitrosamine-induced cancers.