title: 4-Nitroquinoline-1-oxide-induced mutagen sensitivity and risk of nonmelanoma skin cancer: a case-control analysis.
abstract: The UV radiation-mimetic chemical 4-nitroquinoline-1-oxide (4-NQO) is thought to induce squamous cell carcinoma (SCC) similar to those induced by UV radiation in animals. Therefore, we tested the hypothesis that cellular sensitivity to 4-NQO is associated with risk of developing skin cancer in a case-control study of 191 patients with nonmelanoma skin cancer (NMSC; 81 SCC and 110 basal cell carcinoma (BCC)) and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 microM for 24 hours and scored for chromatid breaks in 50 well-spread metaphases. We found that the mean frequency of chromatid breaks per cell (b/c) was significantly higher in the cases (mean+/-SD, 0.46+/-0.43 for SCC and 0.43+/-0.38 for BCC) than in the controls (0.25+/-0.25; P<0.001 for both comparisons) and were associated with more-than-twofold increased risk for both SCC and BCC after adjustment for known risk factors. Therefore, our findings support the notion that sensitivity to 4-NQO reflects susceptibility to UV-induced NMSC. However, there is a lack of correlation between UVB-induced b/c and 4-NQO-induced b/c in this study population. Therefore, these findings need to be verified by additional studies.
authors.affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: T C
authors.initials: TC
authors.lastname: Hsu
authors.forename: Ping
authors.initials: P
authors.lastname: Xiong
authors.forename: Sara S
authors.initials: SS
authors.lastname: Strom
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Gary L
authors.initials: GL
authors.lastname: Clayman
authors.forename: Randal S
authors.initials: RS
authors.lastname: Weber
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Goldberg
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000209:etiology; D002294:Carcinoma, Squamous Cell / Q000209:etiology; D016022:Case-Control Studies; D019457:Chromosome Breakage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009153:Mutagens / Q000633:toxicity*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology*; D014466:Ultraviolet Rays
chemical_list: D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide