SCE induction by cytostatics and its relation to iatrogenic leukemogenesis.

Abstract

There is considerable information currently available about the genotoxic effect, as measured by an alteration in the frequency of sister chromatid exchanges (SCEs), of various environmental chemical compounds (1,13). Evidence is also accumulating on the role of these compounds in carcinogenesis (10) and their ability to induce cytogenetic changes [i.e., chromosomal aberrations (CAs) and SCEs (1,22)]. Considerable information has also been acquired in the* past 10 years about CAs in malignancies, especially hemoblastoses, and there seems to be a close relationship between the location of the break points in specific chromosomal rearrangements and cellular oncogen localization (20). This relationship seems to provide fur ther support to the importance of CA studies in detecting carcinogens, although the role of CAs in tumors and the relationship between the nature of CAs induced by carcinogens and the ones observed in cancer cells remains to be explored. The same lack of understanding, as far as the process of carcinogenesis is concerned, holds true for the relevance of SCEs. Malignant process per se seems not to have an influence on the baseline frequency of SCEs (18), although it is well known that many environmental carcinogens induce SCEs (1) at much lower concentrations of the compounds than is needed for the induction of CAs (16). These marked differences between SCEs and CAs (i.e., their occurrence in malignancies and circumstances of inducibility) underline the fact that SCEs and CAs are different cellular phenomena as far as carcinogenesis and the detection of the genotoxic effects of various compounds are concerned. However, before making any decision as to the relative importance of these two cytogenetical endpoints for mutagenesis and carcinogenesis, one has to realize that most of the studies on CAs have been performed on the tumor tissue, while the information on SCEs in the target tumor tissue is, as yet, very limited (7,17,18).