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 O6-methylguanine (O6MG) 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 O6MG/guanine ratios were determined by HPLC-fluorescence. Mean inhibition of O6MG 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 O6MG formation in liver DNA. Feeding 2.5% garlic for 7 days inhibited DMN-induced O6MG 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.
Zhou
Lin
L
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Mirvish
Sidney S
SS
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004247:DNA / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D004128:Dimethylnitrosamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005737:Garlic / Q000737:chemistry*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D013440:Sulfides; C038491:allyl sulfide; D004247:DNA; C015558:O(6)-methyl-2'-deoxyguanosine; D003849:Deoxyguanosine; D004128:Dimethylnitrosamine