Identification of a subpopulation of MeCCNU resistant cells in previously untreated Lewis lung tumours

Abstract

A variety of experimental endpoints including excision cell survival, lung colony curability, tumour regrowth delay and i.m. tumour curability following MeCCNU alone and combined with gamma-radiation, were used to define the MeCCNU cell survival curve down to "tumour cure" level in previously untreated i.m. Lewis lung tumours. The survival curve was found to be biphasic, the tumour cells being markedly resistant to MeCCNU at high doses of the drug. Below 10 mg kg-1 the survival curve was exponential through the origin with a D10 of approximately 2 mg kg-1, while above 15 mg kg-1 the D10 was approximately 25 mg kg-1. From linear extrapolation of the terminal part of the cell survival curve to zero drug dose, it appeared that about 1 in 10(5) (or 0.001%) of tumour cells were resistant to MeCCNU.