Gimenez-Conti I B, Bianchi A B, Fischer S M, Reiners J J, Conti C J, Slaga T J
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Smithville 78957.
Cancer Res. 1992 Jun 15;52(12):3432-5.
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.
研究了远交系SENCAR小鼠和近交系SENCAR（SSIN）小鼠对多阶段致癌作用的敏感性。使用7,12 - 二甲基苯并[a]蒽或N - 甲基 - N'-硝基 - N - 亚硝基胍作为启动剂，12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯或过氧化苯甲酰作为促进剂诱导肿瘤。尽管每只SSIN小鼠的乳头瘤数量比远交系SENCAR小鼠多，但无论使用何种启动剂或促进剂，在SSIN品系中观察到的癌数量均显著较低。还观察到，SSIN乳头瘤中癌前进展标志物（即发育异常、角蛋白K13表达和角蛋白K1表达缺失）的表达明显受到抑制。在用12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯促进50周后，SSIN小鼠中K13和K1的表达模式与在用12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯促进10至20周后的远交系SENCAR小鼠中观察到的模式相当。还观察到，在SSIN小鼠中由7,12 - 二甲基苯并[a]蒽启动诱导的肿瘤中有67%在Ha - ras - 1基因的第61密码子处发生了突变。后一发现表明，在近交系和远交系之间观察到的肿瘤进展差异与Ha - ras - 1基因的遗传改变无关，而是与我们假设涉及一个假定的抑制基因的独立事件有关。此处报告的数据表明，在SENCAR小鼠品系的选择和近交过程中，赋予肿瘤促进易感性的假定基因与参与肿瘤进展的基因发生了分离。
