The chemotherapeutic drug melphalan induces breakage of chromosomes regions rearranged in secondary leukemia

Abstract

A cytogenetic study is reported on the lesions induced in vitro by melphalan, a currently used anticancer drug. The distribution of 2166 breakpoints shows that they do not occur at random. There is a large excess of breaks in region q1 of chromosome 9 and R bands are significantly more affected than G-band-rich segments. Furthermore, some regions of chromosomes 5, 7, 11, and 17, which are the chromosomes usually rearranged and deleted in secondary leukemias, presumably induced by such treatments, are frequently affected. It is presumed that the frequent involvement of 9q1 largely reflects preexisting monostrand breaks. The frequent breakage of chromosomes 5, 7, 11, and 17 and of R bands in general, which are known to be G-C rich, may result from the preferential methylation of the O6 of guanine by melphalan.