Effects of Caloric Restriction on Aflatoxin B1 Metabolism and DNA Modification in Fischer 344 Rats

Laboratory animals maintained on a reduced calorie, but nutritionally adequate diet have extended life spans and a lowered incidence of spontaneous and chemically induced cancers compared to ad libitum-fed counterparts (Allaben et al., Chapter 4; Kritchevsky and Klurfeld 1987). Results obtained from early studies, such as the pioneering work of Tannenbaum (1942) on the effect of caloric restriction (CR) on mouse skin tumors induced by benzo(a)pyrene, and from the numerous recent studies employing a variety of restriction levels and different carcinogens to induce tumors at different tissue sites (Kritchevsky et al., 1986; Sarkar et al. 1982; Gross 1988; Lagopoulous and Stadler 1987; Newberne and Rogers 1986) demonstrate the profound impact of caloric restriction on tumorigenesis. Although mechanisms underlying the inhibitory effect of CR on carcinogenesis are still not clear, a variety of hypotheses have been proposed which generally focus on the promotion stage (Pariza and Boutwell 1987; Sarkar et al. 1982; Kritchevsky et al. 1984). Recent reports which demonstrate that CR alters xenobiotic metabolizing enzyme activities (Sachan 1982; Sachan and Das 1982; Hasmi et al 1986; Koizumi et al. 1987; Leakey et al. 1989a,b, see also this volume; Table 5.1), decreases 7,12-dimethylbenz(a)anthracene (DMBA) binding to dermal DNA in mice (Pashko and Schwartz 1983), inhibits carcinogenesis induced by indirect- but not direct-acting chemical carcinogens in rats (Pollard and Luckert 1985; Table 5.2), and reduces the binding of aflatoxin B1 (AFB1) to hepatic DNA in rats (Pegram et al. 1989) indicate that in addition to cancer promotion, the initiation of stage of carcinogenesis can be significantly inhibited by CR.