Malignant progression of mouse skin papillomas treated with ethylnitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, or 12-O-tetradecanoylphorbol-13-acetate.
Mouse skin tumors were induced by a single topical application of 7,12-dimethylbenzanthracene (DMBA), followed by biweekly promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). After 20 weeks of promotion, mice were treated twice weekly for 2 weeks with either ethylnitrosourea (ENU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or TPA. Thereafter all groups were treated biweekly with TPA. The ENU-treated group had a higher percentage of animals with carcinomas and developed 217% more cumulative carcinomas per group than TPA-treated controls. The percentage of mice with carcinomas and the cumulative number of carcinomas per group in MNNG-treated mice was higher than TPA-treated controls but was less than ENU-treated mice. The ratio of cumulative carcinomas to cumulative papillomas in ENU treated, MNNG-treated and TPA-treated mice was 16%, 9% and 6%, respectively. Histological examination of tumors remaining at the termination of the experiment revealed the presence of keratoacanthomas, some of which stained positive for gamma-glutamyltransferase (GGT), in the ENU-treated and MNNG-treated, but not the TPA-treated groups. The fact that no new papillomas developed during the progression stage indicated that enhanced carcinogenesis resulted from the progression of pre-existing tumors. Enhanced progression of benign skin tumors in mice by only a few treatments of an agent may serve as a potential model for studies into the mechanisms and the inhibition of malignant progression. The model also allows for a comparison of the potency of agents in enhancing malignant progression.
O'Connell
J F
JF
Klein-Szanto
A J
AJ
Digiovanni
D M
DM
Fries
J W
JW
Slaga
T J
TJ
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D005038:Ethylnitrosourea; D005260:Female; D008769:Methylnitronitrosoguanidine; D051379:Mice; D010212:Papilloma / Q000139:chemically induced* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D008769:Methylnitronitrosoguanidine; D015127:9,10-Dimethyl-1,2-benzanthracene; D005723:gamma-Glutamyltransferase; D013755:Tetradecanoylphorbol Acetate; D005038:Ethylnitrosourea