Carcinogenesis-resistant (Car-R) and carcinogenesis-susceptible (Car-S) mice were obtained applying a bi-directional selective breeding approach to a two-stage skin carcinogenesis protocol, using 9,10-dimethyl-1,2- benzanthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter. Sixteen generations of selection produced a remarkable interline difference in responsiveness to two-stage skin carcinogenesis between Car-R and Car-S: identical DMBA (25 μg) and TPA (5 μg) doses induced papillomas in 100% of Car-S compared with 3.3% of Car-R mice and maximal responses of 14.3 or 0.03 papillomas/mouse, respectively, despite the shorter promotion applied to Car-S (49 vs. 208 days). To define the factors determining this great difference, Car-R and Car-S mice were challenged by initiators/promoters chemically unrelated to those used for selection. Both lines were subjected to either initiation by N-methyl-N-nitrosourea (MNU) followed by TPA promotion, or promotion by benzoyl peroxide, or 1,8- dihydroxy-3-methyl-9-anthrone (chrysarobin) following DMBA initiation. Initiation with MNU induced a 10-fold tumour incidence in Car-S compared with Car-R mice, and a 32-fold difference in tumour induction rate. The 2 lines also differed markedly in susceptibility to benzoyl peroxide promotion: Car-S mice initiated with 25 μg DMBA and promoted with 7.5 mg benzoyl peroxide showed a 12-fold tumour incidence and a 103-fold tumour induction rate compared with the corresponding Car-R group. Both lines, however, were refractory to chrysarobin promotion. The progression of papillomas to carcinomas was examined in all Car-S groups. The incidence of mice that developed carcinomas was 57% in MNU-initiated mice. Benzoyl peroxide was also able to promote carcinoma development in Car-S mice, though with a lower incidence (30.4%) than TPA.
|Pages (from-to)||335 - 340|
|Number of pages||6|
|Journal||International Journal of Cancer|
|Publication status||Published - 1999|
All Science Journal Classification (ASJC) codes
- Cancer Research
Saran, A., Pazzaglia, S., Rebessi, S., Bouthillier, Y., Pioli, C., Covelli, V., ... Biozzi, G. (1999). Skin tumorigenesis by initiators and promoters of different chemical structures in lines of mice selectively bred for resistance (Car-R) or susceptibility (Car-S) to two-stage skin carcinogenesis. International Journal of Cancer, 83(3), 335 - 340. https://doi.org/10.1002/(SICI)1097-0215(19991029)83:3<335::AID-IJC8>3.0.CO;2-W