Length of in vivo exposure to a carcinogenic dose of dimethylnitrosamine necessary for subsequent expression of morphological transformation by rat kidney cells in vitro.

Rat kidney cells isolated in vitro at intervals from one to 24 hours after the administration of a single, carcinogenic dose of dimethylnitrosamine (DMN) were characterized by the expression of morphological transformation and a prolonged life span. In cultures isolated four hours or more following the dose of DMN, morphological transformation was expressed at subculture five, but this effect was progressively delayed with earlier times of isolation. Relative to control kidney cell cultures, transformed cells exhibited enhanced proliferative properties evident from assays for plating efficiency and DNA synthesis. The capacity for increased cloning efficiency by the test cultures was acquired several subcultures after the expression of morphological transformation, while ability for colony formation in semi-solid media evolved later still. The results suggest that target cells permanently altered by the carcinogen are present one hour after the administration of DMN, but the effect is more significant by four hours.