EFFECTS OF DIETARY 1,4-PHENYLENEBIS(METHYLENE)SELENOCYANATE ON ETHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE-INDUCED DNA ADDUCT FORMATION IN LUNG AND LIVER OF A J MICE AND F344 RATS/

1,4-Phenylenebis(methylene)selenocyanate (p-XSC) was tested for its ab ility to inhibit DNA adduct formation induced by the tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the liver and lung of A/J mice and F344 rats, Dietary p-XSC, providing a dose of 5 p.p.m. selenium, significantly inhibited the formation of 7-methylguanine (7-mGua) induced by a single i.p. injection of 10 mu mol of NNK (12.8% inhibition at 4 h and 19.9% at 96 h) and O-6-methylg uanine (O-6-mGua) (16.5% at 4 h and 34.8% at 96 h) in the liver of A/J mice, Dietary supplements of p-XSC providing 15 p.p.m. of selenium re duced the levels of 7-mGua by 17.3% (4 h) and 33.6% (96 h), The format ion of O-6-mGua was inhibited by 69.5% (4 h) and 73.8% (96 h), In A/J mouse lung DNA the most significant reduction was observed in levels o f O-6-mGua, Dietary p-XSC at 5 p.p.m. as selenium inhibited the format ion of this adduct by 73.1% (4 h), Ninety-six hours after NNK injectio n, and at both time points with p-XSC providing 15 p.p.m. selenium, O- 6-mGua was not detected, Although levels of 7-mGua in mouse lung DNA w ere also reduced, this was significant only 4 h after carcinogen admin istration, In general, selenite at 5 p.p.m. as selenium had no signifi cant effect on the levels of these lesions; however, it inhibited O-6- mGua in the liver only 4 h after NNK administration, These effects may explain why there is chemopreventive activity for p-XSC, but not for selenite, in NNK-induced lung carcinogenesis in A/J mice, Moreover, th ese findings raised our interest in determining the potential chemopre ventive activity of p-XSC against NNK-induced lung adenocarcinomas in male F344 rats by first determining its effects on NNK-induced DNA met hylation in the lungs of rats, Diet supplemented with 10 p.p.m. seleni um as p-XSC did indeed inhibit the formation of adducts in pulmonary D NA of F344 rats treated with four consecutive injections of 81 mg/kg o f NNK, Statistically significant inhibition of O-6-mGua formation was observed 4 h after carcinogen treatment in both pulmonary (49.1% inhib ition) and hepatic (39.8%) DNA, Statistically significant inhibition o f 7-mGua formation was also measured in lung DNA isolated 24 h after t he last NNK injection (45.0%) and in liver DNA 4 h after carcinogen tr eatment (31.8%), These results suggest that p-XSC would also inhibit i nduction of lung adenocarcinoma in male F344 rats by NNK.