Modulation of N-nitrosomethylbenzylamine bioactivation by diallyl sulfide in vivo.

摘要: Diallyl sulfide (DAS), a major component of garlic oil, is an inhibitor tumorigenesis by various metabolcally activated carcinogens. In rats, pretreatment with DAS has been observed to suppress completely the induction oesophageal neoplasms N-nitrosomethylbenzylamine (NMBzA) (Wargovich et al. (1988) Cancer Res., 48, 6872-6875). This communication reports effects on overall NMBzA metabolism and DNA methylation in vivo under conditions equivalent single treatment chemoprevention assay. Male Fischer 344 rats received i.g. dose (200 mg/kg body wt) followed s.c. injection [methyl-14C]NMBzA (3.5 mg/kg). controls, exhalation 14CO2 was complete within 5 h (t½max = 1.2 h). 50% injected radioactivity recovered as 14CO2. When given 3 prior [methyl-14C]NMBzA, 49% released 10 administered 18 before carcinogen, 42% converted 14CO2, after 6 1.8 We further examined acute doses 10—200 mg/kg; survival time, h) later. At 200 mg/kg, inhibited formation O6-methyldeoxyguanosine (O6-MEdG) oesophagus (−26%), nasal mucosa (−51%), trachea (−68%) lung (−78%). liver, levels 7-MEdG were reduced 43%. Decreases proportional for >25 oesophagus, liver mucosa, 25—200 10—50 lung. The dose—activity relationship inhibition suggests that short-term modulation carcinogen bioactivation situ contributes but may not be sufficient nitrosamine DAS.