Estimating the Potency of Mutagens: Cytotoxicity as an Obligatory Consequence of Mutagenicity

摘要

Rapid and reliable screening methods are required for identifying environmental mutagens and estimating their mutagenic potency in preparation for use of more elaborate tests to assess the genetic risk to man. On theoretical grounds, one expects a certain minimum cytotoxic potency to correlate with mutagenic potency, particularly when the latter is measured using forward mutations that result in inactive gene products. Furthermore, as cells cannot divide unless a substantial fraction of their genome is functionally intact, mutagenic agents should also be obligatory cytotoxic agents, with a given mutagenicity conferring a certain irreducible cytotoxicity. The authors show here that the cytotoxic potency of 22 chemical mutagens is highly correlated with their mutagenic potency as assayed in five rodent and human in vitro cell systems. This relationship implies that the maximum potential mutagenic potency of such compounds may be reliably estimated from rapid and straightforward measurements of their cytotoxic potency, the latter defined as the failure of cultured cells to undergo continued cell division. The estimate is necessarily a maximum one, as an agent may exert cytotoxic effects by pathways indpendent of its mutagenic action.