1 alpha, 25-dihydroxyvitamin D-3 inhibits hepatic chromosomal aberrations,DNA strand breaks and specific DNA adducts during rat hepatocarcinogenesis

The possible promoting effect of streptozotocin (STZ; 65 mg/kg body weight, intraperitoneal)-induced diabetes during 2-acetylaminofluorene (2-AAF; 0.0 4 % in basal diet)-initiated hepatocarcinogenesis and modulatory effect of 1 alpha ,25-dihydroxyvitamin D-3 (VD3; 0.3 mug/0.1 ml in propylene glycol, per os) were investigated by monitoring chromosomal aberrations (CAs), DNA strand breaks and specific DNA adducts in rat liver. VD3 treatment (twice a week) was started 4 weeks before the 2-AAF regimen and continued throughou t the study. Aberrant metaphase chromosomes were counted from the regenerat ing hepatocytes 15, 30 or 45 weeks after STZ injection, while DNA strand br eak and adduct assays were performed 45 days post-STZ treatment. Dietary ex posure to 2-AAF elicited a substantial increase in CAs and elevated the ext ent of DNA strand breaks and formation of N-(deoxyguanosin-8-yl)-2-aminoflu orene. A promoting effect of STZ was evident from CAs coupled with DNA stra nd break analysis. VD3 treatment substantially reducted 2-AAF+STZ-induced C As as well as DNA strand breaks and adducts. Thus, VD3 appears to be effect ive in suppressing liver-specific early chromosomal as well as DNA damage d uring the process of rat hepatocarcinogenesis initiated with 2-AAF and prom oted by STZ contributing to its promise as a cancer chemotherapeutic agent.