Short-Term Screening Method for the Prediction of Carcinogenicity of Chemical Substances. Current Status and Problems of an in vivo Rodent Micronucleus Assay.

Abstract

Various short-term screening methods have been developed to detect mutagenic/carcinogenic substances. They have played important roles not only in screening suspected chemicals but in studying the mechanisms of mutagenesis/carcinogenesis, and have provided useful information for assessing the genetic effects of chemicals on humans. The micronucleus assay is an in vivo mammalian methods, which has been widely used for screening the genotoxic potency of chemical substances. By this assay, the genotoxicity of chemicals, including clastogens and spindle poisons, have been evaluated using immature bone marrow erythrocytes in mice. The use of immature erythrocytes in circulating peripheral blood instead of in bone marrow of mice has been developed in recent years and it has been determined that it gives results as relevant as those of bone marrow cells in mice. Using the peripheral blood of mice has made the micronucleus assay method more practical and useful. Recently, rats have been identified as an acceptable species for this assay, and assays using the peripheral blood of rats are often carried out concomitantly with general toxicity or carcinogenic studies. However, it must be noted that the micronucleus assays have some limitations. The activity of substances which are metabolized rapidly in mice or rats, for example, may hardly be detected by the micronucleus assay; metabolic features of the substances may affect the assay results greatly. In this review, the current status of the micronucleus assay is discussed as a short-term screening method in the context of its usefulness and its limitations.