Biological dosimetry with cytogenetic endpoints

The induction of chromosome aberrations in the lymphocytes of people who have been exposed to ionizing radiation has provided a much-used quantifiable biological dosimeter with which it is possible to obtain a reliable estimate of the dose of radiation to which the people have been exposed. The induction of aberrations by truly radiomimetic (non-S-dependent) chemicals should also be capable of leading to an estimate of the amount of the chemical that has reached the nuclei of the target cells, and thus give a measure of the damage inflicted. In this case, however, it is not yet possible to relate aberration yield to the initial exposure in a quantifiable manner. Other cytogenetic endpoints, such as micronuclei and sister chromatid exchanges (SCEs), can also be used to estimate whether or not exposures have occurred. Since micronuclei are the result of broken or lagging chromosomes, they too can be used to estimate the dose of ionizing radiation to which a person has been exposed. The use of aberrations or micronuclei for estimating the dose of S-dependent chemicals, however, still remains problematical. SCEs, which are not readily induced by ionizing radiations, have proved to be the most sensitive mammalian endpoint for determining exposure to such S-dependent chemicals. Nevertheless, the utility of SCEs, or any cytogenetic endpoint for that matter, for estimating the dose of any S-dependent chemical has not been shown because of dosimetric problems and because DNA repair can remove many of the adducts before the cells enter S, both of which preclude the use of these endpoints as biological dosimeters for such agents.