Dissociation of sensitivities to tumor promotion and progression in outbred and inbred SENCAR mice.
The sensitivity of outbred SENCAR mice and inbred SENCAR (SSIN) mice to multistage carcinogenesis was studied. Tumors were induced using either 7,12-dimethylbenz[a]anthracene or N-methyl-N'-nitro-N-nitrosoguanidine as initiators and 12-O-tetradecanoylphorbol-13-acetate or benzoyl peroxide as promoting agents. Although the number of papillomas per mouse was higher in SSIN than in outbred SENCAR mice, the number of carcinomas observed in the SSIN strain was significantly lower regardless of the initiator or promoter used. It was also observed that the expression of markers of premalignant progression (i.e., dysplasia, expression of keratin K13, and loss of keratin K1 expression) was markedly suppressed in SSIN papillomas. After 50 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate, the pattern of expression of K13 and K1 in SSIN mice was comparable to the pattern observed in outbred SENCAR mice after 10 to 20 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate. It was also observed that 67% of the tumors induced in SSIN mice by initiation with 7,12-dimethylbenz[a]anthracene exhibited a mutation in codon 61 of the Ha-ras-1 gene. This latter finding suggests that the differences observed in tumor progression between the inbred strain and the outbred stock are not related to a genetic alteration in the Ha-ras-1 gene but rather to an independent event that we have postulated to involve a putative suppressor gene. The data reported here suggest that the putative gene(s) that confers susceptibility to tumor promotion was segregated from the gene(s) involved in tumor progression during selection and inbreeding of the SENCAR mouse stock.
Gimenez-Conti
I B
IB
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Smithville 78957.
Bianchi
A B
AB
Fischer
S M
SM
Reiners
J J
JJ
Conti
C J
CJ
Slaga
T J
TJ
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001585:Benzoyl Peroxide; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000737:chemistry / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics; D007633:Keratins / Q000032:analysis; D008769:Methylnitronitrosoguanidine; D051379:Mice; D009154:Mutation; D010212:Papilloma / Q000139:chemically induced* / Q000737:chemistry / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000235:genetics; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate
D008769:Methylnitronitrosoguanidine; D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins; D013755:Tetradecanoylphorbol Acetate; D001585:Benzoyl Peroxide