Correlation between the half-wave reduction potentials of nitroheterocycles and their mutagenicity in Chinese hamster V79 spheroids

Abstract

Toxicity and DNA damage by nitroheterocycles has previously been correlated with their redox potentials. Resistance to 6-thioguanine was measured using Chinese hamster V79 cells grown in suspension culture as three-dimensional cell clusters of “spheroids”. Since diffusion gradients of oxygen and other nutrients are largely responsible for the growth properties of spheroids, cells grown as spheroids might better simulate cells exposed to mutagens in vivo. The log of the concentration inducing 10 mutants/plate or 1.6 × 10 5 clonogenic cells from spheroids (equivalent to about 300 rad), was correlated with the half-wave reduction potential of a series of nitroheterocycles. FANFT and 4NQO were more mutagenic than predicted on the basis of redox potential.