Mechanisms for induction of mutations and chromosome alterations

Genotoxic agents induce chromosomal alterations, such as aberrations, micronuclei, and sister chromatid exchanges as well as mutations both in vivo and in vitro. Ionizing radiation and typical radiomimmetic agents such as bleomycin are very efficient inducers of chromosomal aberrations. The type of aberrations induced by these agents are cell-cycle dependent, i.e., chromosome type in pre-replication stages and chromatid type in post-replication stages of the cell cycle. Under optimal DNA repair conditions, DNA double-strand breaks (DSBs) appear to be the most important lesion responsible for the production of aberrations. In human lymphocytes, fast-repairing DSBs lead to exchange-type aberrations. The fact that the dose-response curves for induction of exchange aberrations induced by ionizing radiation are similar in vitro and in vivo allows one to use the yield of induced aberrations to estimate absorbed radiation dose in the case of accidents. In this respect, frequencies of translocations detected by the chromosome painting technique appear to be more sensitive. Mutations do not express immediately after exposure and require an expression time before they can be detected. In humans, it is estimated that for the mutations induced in bone marrow, it takes about 2 months for them to express and to be detected in peripheral blood lymphocytes. Hence, frequency of mutations is of limited value for estimating radiation doses immediately after an accident. This holds true for chemical exposure as well.(ABSTRACT TRUNCATED AT 250 WORDS)