The possible promoting effect of
streptozotocin (STZ; 65 mg/kg
body weight, intraperitoneal)-induced diabetes during
2-acetylaminofluorene (2-AAF; 0.04% in basal diet)-initiated hepatocarcinogenesis and modulatory effect of 1alpha,25-dihydroxyvitamin D3 (VD3; 0.3 microg/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 throughout the study. Aberrant metaphase chromosomes were counted from the regenerating hepatocytes 15, 30 or 45 weeks after STZ injection, while
DNA strand break and adduct assays were performed 45 days post-STZ treatment. Dietary exposure to
2-AAF elicited a substantial increase in CAs and elevated the extent of
DNA strand breaks and formation of
N-(deoxyguanosin-8-yl)-2-aminofluorene. A promoting effect of STZ was evident from CAs coupled with
DNA strand break analysis. VD3 treatment substantially reducted 2-AAF+STZ-induced CAs as well as
DNA strand breaks and adducts. Thus, VD3 appears to be effective in suppressing liver-specific early chromosomal as well as DNA damage during the process of rat hepatocarcinogenesis initiated with
2-AAF and promoted by STZ contributing to its promise as a
cancer chemotherapeutic agent.