Presensitization of human cells with extrinsic signals to induced chemical carcinogenesis.

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 B1 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 B1 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.