Presensitization of human cells with extrinsic signals to induced chemical carcinogenesis

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Abstract
Foreskin‐derived low‐passage human cell populations were reproducibly transformed with chemical carcinogens when the cells were blocked in G1, released from the block, and treated with either the carcinogen N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG) or with Aflatoxin BI in the S period of the cell cycle. Arginine‐and glutamine‐deficient medium was required to effectively block the cells in the G1 period. Estradiol, insulin, anthralin or phorbol myristate acetate sensitized the cell population to carcinogen treatment when added 10 h before the carcinogen in early S period. Presensitized cells kept blocked in G1 period for 48 h or longer, released and treated in S period with MNNG or Aflatoxin BI were not transformed; nor did transformation occur in presensitized cell populations treated in G2 (4.5 h), M (1.5 h) or G1 (8.2 h). Cells derived from carcinogen‐treated presensitized cells grew as colonies in soft agar at 16‐20 PDL. When cells derived from colonies isolated from the soft agar were injected subcutaneously into nude mice, tumors developed.

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