Genotoxicity of DNA Intercalating Anticancer Drugs: Pyrimido[4(I),5(I):4,5] thieno(2,3-b)quinolines on Somatic and Germinal Cells

Abstract

ABSTRACT The genotoxic effect of the anticancer drugs Oxo-PTQ, Morpholino-PTQ, and Chloro-PTQ were studied in mice bone marrow by means of chromosome aberrations and micronucleus assay. These drugs, at dose levels of 21.42, 28.57, and 35.71 mg/kg b.w., respectively, were given to mice in a single application via the intraperitoneal route. Marrow was collected at 24, 48, and 72 h after the application. The chromosome aberrations and micronucleus assay were done according to standard procedures. These compounds gave rise to an increase in the number of micronuclei in a dose-dependent manner. The number of micronucleated polychromatic erythrocytes showed a maximum at 24 h, and there was partial recovery at 72 h. Chromosome aberrations increased significantly as compared to normal controls when treated with Oxo-PTQ followed by Morpholino-PTQ at 21.42 mg/kg b.w. (48 h). Statistically significant sperm abnormalities also revealed the genotoxic potency of these drugs. Our results suggest that the Pyrimido[4(I),5(I):4,5]thieno(2,3-b)quinoline drugs owe at least some of their cytotoxicity to their genotoxic effects, which seem to be mediated through interaction with topoisomerase II.