β-carotene inhibits rat liver chromosomal aberrations and DNA chain break after a single injection of diethylnitrosamine

Abstract

Beta-carotene (BC) has recently been found to possess potent anti-tumour activity in chemically induced rat liver carcinogenesis. In the present study, attempts have been made to understand the basic cytogenetic and molecular mechanism of the anti-tumour effect of BC by monitoring its effect on rat liver chromosomal aberrations (CAs) and DNA chain breaks during the early preneoplastic stage of diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male rats. DNA chain breaks, however, can be detected with great sensitivity by exposing crude cell lysates to alkaline solutions and monitoring the rate of strand unwinding so that one strand break per chromosome can easily be detected. Supplementary BC, in basal diet (120 mg kg[-1]), was given to rats 15 days before carcinogenic threat with DEN. Under these experimental conditions, BC was found to afford a unique protection against DEN-induced CAs 96 h after DEN injection. Long-term treatment with BC also triggered a protective effect on induction of CAs 15, 30 or 45 days after DEN treatment, which was maximal on structural aberrations followed by numerical and physiological types. BC treatment for 15 days before DEN injection was found to offer a significant (P < 0.001) protection in the generation of single-strand breaks compared with DEN control. Thus, BC ranks as a potential chemopreventive agent for the future so far as chemical rat liver carcinogenesis is concerned.