Initiation of C3H/10T1/2 cell transformation by formaldehyde.

The effects of formaldehyde were evaluated in the C3H/10T1/2 Cl 8 cell transformation system. Treatment of the cells with 0.1-2.5 micrograms/ml for formaldehyde alone did not result in significant rates of transformation. If formaldehyde treatment was followed by continuous treatment with 0.1 microgram/ml of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), transformed foci were produced. Methanol and formic acid lacked significant transforming activity under either treatment regimen. The results suggest that formaldehyde is an initiating agent for C3H/10T1/2 Cl 8 transformation. The fact that some compounds may act solely as initiators should be considered when this transformation system is used to study chemicals which may interact with cells by mechanisms similar to that of formaldehyde.

Initiation of C3H/10T1/2 cell transformation by N-methyl-N'-nitro-N-nitrosoguanidine and aflatoxin B1.

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.