Comparison of 7,12-dimethylbenz(a)anthracene-DNA adduction in the epidermis of two lines of mice selected for resistance (CAR-R) or susceptibility (CAR-S) to skin carcinogenesis.
Two lines of mice were produced by bidirectional selective breeding: one resistant (CAR-R) and one susceptible (CAR-S) to two-stage skin carcinogenesis by dimethylbenz(a)anthracene and 12-O-tetradecanoyl-phorbol-13-acetate. The dimethylbenz(a)anthracene-DNA adduct formation was compared in the two lines by a postlabeling procedure so as to determine whether the striking interline difference observed as to tumor incidence could (in part) be due to differences in the formation of DNA-reactive metabolites. Results show that qualitatively, adduct profiles in CAR-R and CAR-S epidermis are similar. Quantitatively, the total binding level is slightly higher in CAR-S versus CAR-R mice during the 30-day follow-up. However, these minor differences do not increase in function of the response to selection observed through three consecutive generations. A 2- or 4-week promotion with 12-O-tetradecanoylphorbol-13-acetate enhances the decrease of adduct level in the two lines. This effect is somewhat more pronounced in CAR-S mice. Results strongly suggest that the expression of the genes responsible for CAR-R/CAR-S phenotypic difference affects mainly the postinitiation stages.
Perin
F
F
Service de Génotoxicité et Cancérogénèse, Institut Curie, Orsay, France.
Perin
O
O
Barat
N
N
Plessis
M J
MJ
Saran
A
A
Pioli
C
C
Covelli
V
V
Biozzi
G
G
Mouton
D
D
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D004351:Drug Resistance; D004817:Epidermis / Q000378:metabolism; D005260:Female; D051379:Mice; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; D018736:DNA Adducts; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D013755:Tetradecanoylphorbol Acetate