Effects of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) and Vitamin E on 4-nitroquinoline-N-oxide (4-NQO)-induced mutagenesis in lacZ mouse upper aerodigestive tissue

The effects of dietary administration of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) and Vitamin E on 4-nitroquinoline-N-oxide (4-NQO)-induced mutagenesis in lacZ mouse upper aerodigestive tissues were investigated. 4-NQO was a potent mutagen in tongue, other pooled oral tissues and esophagus when given in drinking water for 4 weeks at a concentration of 20mg/ml. The mutant fractions (MFs) in these tissues were: 144±73, 130±52 and 61±24 mutants/10⁵, respectively. Background levels were 3.7±1.9 in tongue, 2.9±1.2 in esophagus and 2.4±1.0 in pooled oral tissue. Vitamin E at levels of 200 and 400IU/kg diet led to no significant effects on mutagenesis although a small decrease in the MF was observed in all tissues at the higher dose. Dietary p-XSC at levels of 2.5 and 10ppm selenium also resulted in no statistically significant effects on mutagenesis, but mutagenesis was somewhat reduced in esophagus and pooled oral tissue at the higher dose. However, the combination of the low doses of p-XSC and Vitamin E resulted in nearly a 40% decrease in mutagenesis in tongue and esophagus, and this decrease was statistically significant (P=0.008 and 0.023, respectively. No inhibition was observed using a combination of the higher doses of p-XSC and Vitamin E. These results lend support to the use of low doses of inhibitors of mutagenesis in combinations. The application of in vivo mutagenesis assays to the screening of chemopreventive agents enables investigators to evaluate potential inhibitors when given individually and in combinations on the initiation stage of carcinogenesis in a short-term in vivo bioassay.