Boreiko C J, Ragan D L, Abernethy D J, Frazelle J H
Carcinogenesis. 1982;3(4):391-5. doi: 10.1093/carcin/3.4.391.
The utility of C3/H/10T1/2 mouse embryo fibroblasts for the detection of carcinogenic substances has been limited by their apparent insensitivity to the oncogenic effects of direct-acting alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and procarcinogens such as aflatoxin B1 (AFB1). Because the process of C3H/10T1/2 transformation can be observed to proceed through discrete stages of initiation and promotion, we have considered the possibility that MNNG and AfB1 may only initiate C3H/10T1/2 transformation. Treatment of asynchronous C3H/10T1/2 cells with MNNG or AfB1 alone generally produced few transformed foci. If MNNG or AfB1 treatment was followed by the exposure of cells to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), numerous transformed foci were produced. Phorbol did not enhance transformation by either substance. MNNG and AfB1 thus appear to be initiating agents for transformation. TPA also enhanced the transformation of C3H/10T1/2 cells by low doses of 3-methylcholanthrene (3-MCA), but transformation by high concentrations of 3-MCA was inhibited by the presence of TPA. These studied suggest that the sensitivity of the C3H/10T1/2 transformation system to potential carcinogens can be dramatically heightened if the bioassay is conducted in the presence and absence of TPA.
C3H/10T1/2小鼠胚胎成纤维细胞用于检测致癌物质的效用一直受到限制，因为它们对诸如N-甲基-N'-硝基-N-亚硝基胍（MNNG）等直接作用的烷基化剂以及诸如黄曲霉毒素B1（AFB1）等前致癌物的致癌作用明显不敏感。由于可以观察到C3H/10T1/2细胞转化过程是通过起始和促进的离散阶段进行的，我们考虑了MNNG和AFB1可能仅引发C3H/10T1/2细胞转化的可能性。单独用MNNG或AFB1处理异步C3H/10T1/2细胞通常产生很少的转化灶。如果在MNNG或AFB1处理后将细胞暴露于肿瘤促进剂12-O-十四烷酰佛波醇-13-乙酸酯（TPA），则会产生大量转化灶。佛波醇不会增强这两种物质的转化作用。因此，MNNG和AFB1似乎是细胞转化的起始剂。TPA还增强了低剂量3-甲基胆蒽（3-MCA）对C3H/10T1/2细胞的转化作用，但高浓度3-MCA的转化作用会受到TPA的抑制。这些研究表明，如果在有和没有TPA的情况下进行生物测定，C3H/10T1/2细胞转化系统对潜在致癌物的敏感性会显著提高。
