Short-term tests for transplacentally active carcinogens A comparison of sister-chromatid exchange and the micronucleus test in mouse foetal liver erythroblasts

Chromatin proteins are covalently modified by at least five different processes; in no case has the precise physiological function been established. One of these post-synthetic, covalent modifications is effected by the enzyme poly(ADP-ribose) polymerase, which uses the coenzyme NAD+ to ADP-ribosylate chromatin proteins. The modification consists largely of mono(ADP-ribose), but long, homopolymer chains of (ADP-ribose) are also present. Various physiological functions have been suggested for (ADP-ribose)n. Here we demonstrate that one function of (ADP-ribose)n is to participate in the cellular recovery from DNA damage. Specific inhibitors of poly(ADP-ribose) polymerase prevent rejoining of DNA strand breaks caused by dimethyl sulphate and cytotoxicity is enhanced thereby. The rejoining of strand breaks is prevented also by nutritionally depleting the cells of NAD.

A staining technique that detects sister chromatid exchanges (SCEs) has been used to examine the response of chromosomes in cultured Chinese hamster cells to a wide variety of mutagens-carcinogens. The test gives a very sensitive and rapid method for detecting chromosome mutagenicity of chemical agents and provides a powerful new method for detecting environmental mutagens.

The effects of a number of chemicals on sister-chromatid exchange (SCE) frequencies in in vivo and in vitro systems are reviewed. Standardized protocols for future SCE testing in important systems, as well as for evaluation of test results, are presented. Data reported thus far suggest that SCE analysis may prove useful, especially at a secondary level, as a test of mutagenic carcinogens. Strengths and limitations of SCE analysis are summarized as a guide for future evaluation and use of this procedure.