The cytokinesis-block micronucleus technique and its application to genotoxicity studies in human populations.

Abstract

The development of the cytokinesis-block (CB) technique has made the human lymphocyte micronucleus assay (MN) a reliable and precise method for assessing chromosome damage. Recent studies in our laboratory have confirmed that this method is a sensitive indicator of in vivo radiation exposure in patients undergoing fractionated partial-body radiotherapy and rodents exposed to uniform whole-body irradiation, thus supporting the application of the cytokinesis-block micronucleus (CBMN) assay for biological dosimetry. To further define the use of this assay in biomonitoring, we have also undertaken extensive studies to determine the spontaneous level of MN in normal human populations and its relationship to various lifestyle factors. During the past year, we have also developed a new variation to the CBMN assay that enables the conversion of excision-repairable lesions to MN within one cell-cycle using cytosine arabinoside. With this method the slope of the in vitro dose-response curves was increased by a factor of 1.8 for X-rays, 10.3 for ultraviolet (254 nm) radiation, and approximately 40-fold for methylnitrosourea. Consequently, the CBMN assay can now be used not only to measure whole chromosome loss or chromosome breaks but also excision repair events. The versatility and simplicity of the CBMN assay together with new developments in automation should enable its successful application in monitoring exposed populations as well as identifying mutagen-sensitive individuals within a population.