Effect of lead chromate on chromosome aberration, sister-chromatid exchange and DNA damage in mammalian cells in vitro.

Possible mutagenic activity of lead chromate in mammalian cells was studied using assays for chromosome aberrations and sister-chromatid exchanges in cultured human lymphocytes, and DNA fragmentation as detected by alkaline-sucrose gradient sedimentation in cultured Chinese hamster ovary (CHO) cells. Lead chromate caused dose-related increases in chromosome aberration and sister-chromatid exchange in human lymphocytes. No increase in DNA damage was observed in CHO cells, possibly due to the relative insensitivity of the CHO cells and the limited solubility of lead chromate in tissue culture medium. The mutagenicity of lead chromate in human lymphocytes appears to be entirely due to the chromate ion since chromosome aberrations were induced by potassium chromate but not lead chloride.

Detection of the mutagenic activity of lead chromate using a battery of microbial tests.

The potential mutagenicity of the carcinogen lead chromate was tested by the following battery of microbial tests: the Escherichia coli PolA+/PolA- survival test; the Salmonella/microsome His+ reversion assay; the E. coli Trp+ reversion test as a plate assay; the E. coli Gal+ forward mutation test; and the Saccharomyces cerevisiae assay for mitotic recombination. Lead chromate is mutagenic in Salmonella and in Saccharomyces and is thus identified as a microbial mutagen by this battery. Metabolic activation by rat liver homogenate (S9) is not required for the mutagenic activity of lead chromate. The most statistically significant, positive result is found with a supplementary assay, the E. coli fluctuation test. To determine whether the lead ion and/or the chromate ion were responsible for the mutagenicity observed, lead chloride and chromium trioxide (chromic acid) were also tested. In E. coli fluctuation test, the ranges of maximal mutagenicity for chromium trioxide and lead chromate overlap at the concentration 10(-5)M, whereas lead chloride shows no mutagenicity and little lethality at concentrations up to 10(-3)M. Thus, it appears that the chromate ion is responsible for the mutagenicity of lead chromate.

A hierarchical approach to mutagenicity testing and regulatory control of environmental chemicals.

A hierarchical approach to mutagenicity testing and regulatory control of environmental chemicals is proposed. The guiding concepts and principles relating to the testing of chemicals for mutagenicity and evaluation of genetic hazards are discussed.

International reference study on the identification and scoring of human chromosome aberrations. Results of a WHO comparative study.

Chromosome aberrations in human peripheral blood are recognized parameters of cellular damage and are used as indicators of exposure to ionizing radiation and certain chemicals. However, significant interlaboratory variability exists in the results reported from different laboratories. The primary objective of the present study was to examine problems associated with the identification and analysis of chromosome aberrations. Significant interlaboratory variability was found to exist in the analysis of human chromosome spreads for induced interphase aberrations, apparently owing in part to differences in the selection and rejection of spreads for scoring and also in the recognition and classification of various types of aberrations. These differences are reflected in the dose-response relationships for aberrations as well as for damaged spreads. For damaged spreads the scoring variability appears to be relatively small. It is inferred that factors additional to differences in scoring may play a significant role in the large variation in the reported dose-response relationships both for ionizing radiation and for chemically induced aberrations.