Relationships between in vitro mutagenicity assays.

Abstract

This paper analyzes the mutagenicity results reported by the US National Toxicology Program (NTP), relative to 41 chemicals assayed with four in vitro short-term tests [Salmonella typhimurium (STY), Chromosomal aberrations in Chinese hamster ovary (CHO) cells (CHA), Sister chromatid exchange in CHO cells (SCE), mutation in L5178Y mouse lymphoma cells (MLY)] and puts this database in perspective with respect to other databases. It is shown that the test relationships pointed out by the experiments on the 41 chemicals are in substantial agreement with those indicated by a previous NTP report on 73 chemicals, and that the same test relationships were also indicated by the results on the International Program for the Evaluation of Short-Term Tests for Carcinogens (IPESTTC). The NTP and IPESTTC databases consistently indicated that there is a gradual increase in the sensitivity to the genotoxins in the following order: STY < CHA < SCE < MLY. On this scale, SCE and MLY show a great degree of similarity of responses to the chemicals, as does STY with CHA. The overall evidence provided by these results, and by the general pattern of IPESTTC and NTP genotoxicity profiles, does not support the notion that the genotoxic chemicals have genetic end point specificity. Moreover, a mathematical simulation analysis demonstrated that MLY and SCE--the two most sensitive assays of those studied by NTP--are not more subject to erratic results than other assays, and that they form--together with STY and CHA--a consistent family of genotoxicity assays.