Mutagenic activity of 4-nitroquinoline-N-oxide in upper aerodigestive tissue in lacZ mice (Muta (TM) Mouse) and the effects of 1,4-phenylenebis(methylene)selenocyanate

4-Nitroquinoline-N-oxide (4-NQO) was administered to lacZ mice at a concent ration of 20 mu g/ml in drinking water for 2 weeks, and the mutagenic fract ions in a number of organs were assayed. The mutant fractions in tongue, es ophagus and other pooled oral tissues were, respectively, 117 +/- 26, 73 +/ - 15, and 48 +/- 15 mutants/10(5) plaque-forming units (pfu) (ca. 15-40 x b ackground). 4-NQO was not mutagenic in lung, liver or colon at conditions u sed here. We had previously demonstrated that the synthetic organoselenium compound, 1,4-phenylenebis(methylene)selenocyanate (p-XSC), an established chemopreventive agent, greatly reduced carcinogenicity in 4-NQO in rat tong ue, and we observed here that administration of p-XSC (10 ppm se) in the di et for 6 weeks (2 weeks before, during, and 2 weeks after 4-NQO) resulted i n a 33% decrease in mutagenesis in oral tissue, a 17% decrease in esophagus , and a slight increase in tongue. Only the decrease in oral tissue reached statistical significance (p < 0.04). The results reported here demonstrate that 4-NQO was extremely mutagenic in lacZ mouse tongue, with lower, but h ighly significant activities in esophagus and other pooled oral tissues. Th e high activity of 4-NQO in lacZ mouse tongue is consistent with the organ specificity of 4-NQO in the rat. Inhibition of 4-NQO-induced mutagenesis by p-XSC was observed mainly in pooled oral tissues, other than tongue. Possi ble reasons for the difference between inhibition of mutagenesis and carcin ogenesis in tongue are discussed, as well as advantages and disadvantages o f in vivo mutagenesis assays as surrogates for carcinogenicity assays in ch emoprevention studies. (C) 2000 Published by Elsevier Science B.V. All righ ts reserved.