| Abstract
| - The ability of rat tissues to activate the esophageal carcinogen,N-nitrosobenzylmethylamine(NBzMA), to a DNA benzylating intermediate was investigated.[3-3H]NBzMA was preparedand given to male F344 rats. Tissues were harvested 4 h aftertreatment, and DNA wasisolated. HPLC analysis with radiochemical detection of chemicaland enzymatic hydrolysatesof DNA from liver and lung revealed the formation of benzyl adducts.Benzyl alcohol,N2-benzylguanine, 3-benzyladenine,N6-benzyladenine, and 7-benzylguanine were themajorradioactive components in the hydrolysates. An unknown adduct wasalso observed. Theadduct distribution was similar to that observed in[3-3H]benzylnitrosourea([3-3H]BzNU)-treated calf thymus DNA. However, enzymatic hydrolysates of[3-3H]BzNU-treated DNA alsocontained significant levels ofO6-benzyl-2‘-deoxyguanosine(O6-BzdG). This radioactiveadductdisappeared upon incubation of the DNA with a crude preparation of therepair protein,O6-alkylguanine−DNA alkyltransferase isolatedfrom rat liver. These data provide evidencethat O6-BzdG is probably rapidly repairedin vivo. No benzylation of esophageal mucosalDNAwas detected. The level of DNA benzylation observed in tissuesfrom [3-3H]NBzMA-treatedrats was several orders of magnitude lower than the level of DNAmethylation in these sametissues. Therefore, these data indicate that DNA benzylation playsa minor role, if any, in thecarcinogenic activity of NBzMA.
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