Mutagenic activity of 4-nitroquinoline-N-oxide in upper aerodigestive tissue in lacZ mice (MutaMouse) and the effects of 1, 4-phenylenebis(methylene)selenocyanate.
4-Nitroquinoline-N-oxide (4-NQO) was administered to lacZ mice at a concentration of 20 microg/ml in drinking water for 2 weeks, and the mutagenic fractions in a number of organs were assayed. The mutant fractions in tongue, esophagus and other pooled oral tissues were, respectively, 117+/-26, 73+/-15, and 48+/-15 mutants/10(5) plaque-forming units (pfu) (ca. 15-40xbackground). 4-NQO was not mutagenic in lung, liver or colon at conditions used 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 tongue, and we observed here that administration of p-XSC (10 ppm se) in the diet for 6 weeks (2 weeks before, during, and 2 weeks after 4-NQO) resulted in 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 highly significant activities in esophagus and other pooled oral tissues. The 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. Possible reasons for the difference between inhibition of mutagenesis and carcinogenesis in tongue are discussed, as well as advantages and disadvantages of in vivo mutagenesis assays as surrogates for carcinogenicity assays in chemoprevention studies.
von Pressentin
M M
MM
Division of Basic Sciences/Biochemistry, New York University, Dental Center, 345 E. 24th Street, New York, NY 10100, USA.
El-Bayoumy
K
K
Guttenplan
J B
JB
D015112:4-Nitroquinoline-1-oxide / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001435:Bacteriophages / Q000235:genetics; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009055:Mouth / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000008:administration & dosage* / Q000633:toxicity; D009154:Mutation; D016566:Organoselenium Compounds / Q000494:pharmacology*; D014059:Tongue / Q000187:drug effects / Q000378:metabolism
D016588:Anticarcinogenic Agents; D009153:Mutagens; D016566:Organoselenium Compounds; D015112:4-Nitroquinoline-1-oxide; C074153:1,4-phenylenebis(methylene)selenocyanate; D004247:DNA