Induction of unscheduled DNA synthesis in hairless mouse epidermis by skin carcinogens.
Induction of unscheduled DNA synthesis (UDS) in hairless mouse epidermis by six chemicals was determined in an in vivo-in vitro assay by using a liquid scintillation counting method. Test chemicals were applied once onto two areas of the back of female hairless mice after stripping of the stratum corneum with adhesive tape to enhance skin penetration. After exposure, the skin samples were taken and cultured in a medium containing [3H]thymidine with or without hydroxyurea (HU, an inhibitor of replicative DNA synthesis). DNA of the epidermis was extracted, and incorporation of [3H]thymidine into DNA and the DNA content was determined with a liquid scintillation counter and a fluorescence spectrophotometer, respectively. Induction of UDS by chemicals was judged by calculation of the UDS index [(the ratio of DNA synthesis in the presence of HU to that in its absence) x 100]. A good correlation between UDS induction and organ specificity of carcinogens was observed. 4-Nitroquinoline 1-oxide, a skin carcinogen used as a positive control, induced a dose-dependent increase in the UDS index of approximately 12-fold at 2 hr after exposure, while 1,2-epoxydodecane, a non-skin carcinogen applied as a negative control, did not increase the UDS index. Four other skin carcinogens induced dose-dependent increases in the UDS index; N-methyl-N'-nitro-N-nitrosoguanidine and diepoxybutane at 2 hr after exposure, and 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene at 24 hr after exposure. The results suggest that UDS is a good marker of the genotoxicity of skin carcinogens.
Mori
M
M
Life Science Research Center, Shiseido Co., Ltd., Kanagawa, Japan.
Kobayashi
H
H
Sugiyama
C
C
Katsumura
Y
Y
Furihata
C
C
D015112:4-Nitroquinoline-1-oxide / Q000031:analogs & derivatives / Q000633:toxicity; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D004247:DNA / Q000032:analysis / Q000096:biosynthesis*; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000633:toxicity; D005260:Female; D006918:Hydroxyurea / Q000633:toxicity; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D051379:Mice; D008812:Mice, Hairless; D015363:Quinolones / Q000633:toxicity; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
C120195:4-nitroquinolone-1-oxide; D002273:Carcinogens; D004852:Epoxy Compounds; D015363:Quinolones; D008769:Methylnitronitrosoguanidine; D001564:Benzo(a)pyrene; D015112:4-Nitroquinoline-1-oxide; D015127:9,10-Dimethyl-1,2-benzanthracene; C007366:diepoxybutane; D004247:DNA; D006918:Hydroxyurea