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

Marcia D.M. Von Pressentin, Karam El-Bayoumy, Joseph B. Guttenplan

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

4-Nitroquinoline-N-oxide (4-NQO) was administered to lacZ mice at a concentration of 20 μg/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/105 plaque-forming units (pfu) (ca. 15-40 x background). 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. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume466
Issue number1
DOIs
StatePublished - Mar 3 2000

Fingerprint

4-Nitroquinoline-1-oxide
Tongue
Mutagenesis
Esophagus
Organoselenium Compounds
Organ Specificity
1,4-phenylenebis(methylene)selenocyanate
Chemoprevention
Drinking Water
Colon
Carcinogenesis
Diet
Lung

All Science Journal Classification (ASJC) codes

  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

@article{9e797e968a514f10b83ad7bd03b303e2,
title = "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",
abstract = "4-Nitroquinoline-N-oxide (4-NQO) was administered to lacZ mice at a concentration of 20 μg/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/105 plaque-forming units (pfu) (ca. 15-40 x background). 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. (C) 2000 Elsevier Science B.V.",
author = "{Von Pressentin}, {Marcia D.M.} and Karam El-Bayoumy and Guttenplan, {Joseph B.}",
year = "2000",
month = "3",
day = "3",
doi = "10.1016/S1383-5718(00)00005-X",
language = "English (US)",
volume = "466",
pages = "71--78",
journal = "Mutation Research - Genetic Toxicology and Environmental Mutagenesis",
issn = "1383-5718",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - 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

AU - Von Pressentin, Marcia D.M.

AU - El-Bayoumy, Karam

AU - Guttenplan, Joseph B.

PY - 2000/3/3

Y1 - 2000/3/3

N2 - 4-Nitroquinoline-N-oxide (4-NQO) was administered to lacZ mice at a concentration of 20 μg/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/105 plaque-forming units (pfu) (ca. 15-40 x background). 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. (C) 2000 Elsevier Science B.V.

AB - 4-Nitroquinoline-N-oxide (4-NQO) was administered to lacZ mice at a concentration of 20 μg/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/105 plaque-forming units (pfu) (ca. 15-40 x background). 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. (C) 2000 Elsevier Science B.V.

UR - http://www.scopus.com/inward/record.url?scp=0034599054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034599054&partnerID=8YFLogxK

U2 - 10.1016/S1383-5718(00)00005-X

DO - 10.1016/S1383-5718(00)00005-X

M3 - Article

C2 - 10751728

AN - SCOPUS:0034599054

VL - 466

SP - 71

EP - 78

JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

SN - 1383-5718

IS - 1

ER -