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 l...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-09, Vol.54 (17), p.4635-4640
Main Authors: PERIN, F, PERIN, O, BARAT, N, PLESSIS, M.-J, SARAN, A, PIOLI, C, COVELLI, V, BIOZZI, G, MOUTON, D
Format: Article
Language:English
Subjects:
9,10-Dimethyl-1,2-benzanthracene - analogs & derivatives
9,10-Dimethyl-1,2-benzanthracene - metabolism
Animals
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Cell Line
Chemical agents
DNA - metabolism
DNA Adducts
Drug Resistance
Epidermis - metabolism
Female
Medical sciences
Mice
Skin - metabolism
Skin Neoplasms - chemically induced
Tetradecanoylphorbol Acetate - pharmacology
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445