The Journal of Nutrition Vol. 127 No. 2 February 1997, pp. 210-217
Copyright ©1997 by the American Society for Nutritional Sciences

Food Restriction Reduces Aflatoxin B₁ (AFB₁)-DNA Adduct Formation, AFB₁-Glutathione Conjugation, and DNA Damage in AFB₁-Treated Male F344 Rats and B6C3F₁ Mice

Manuscript received 29 January 1996. Initial reviews completed 19 March 1996. Revision accepted 3 October 1996.

Division of Nutritional Toxicology, National Center for Toxicological Research, Jefferson, AR 72079

The objective of this study was to examine effects of food restriction (FR) on the metabolic activation of aflatoxin B₁ (AFB₁) in rats and mice, which are AFB₁-sensitive and -resistant rodent species, respectively. Forty percent FR [60% of ad libitum (AL) food consumption] reduced the metabolic activation of AFB₁ in both rats and mice, causing formation of hepatic AFB₁-DNA adducts to be 43% and 31% lower, respectively. The AFB₁-DNA adduct 8,9-dihydro-8-(N⁷-guanyl)-9-hydroxyaflatoxin B₁ (AFB₁-N⁷-Gua) was predominantly formed in rat liver DNA; the formation of the ring-open analogue of AFB₁-N⁷-Gua, AFB₁-formamidopyrimidine (AFB₁-FAP), was predominantly found in mouse liver DNA. In contrast to the in vivo results, the in vitro AFB₁-DNA adduct formation mediated by the microsomes of liver, kidney or lung from FR-mice was greater than the formation of AFB₁-DNA adducts mediated by the tissue microsomes from the AL-mice. Food restriction induced hepatic glutathione S-transferase (GST) activity, as measured by the formation of AFB₁-glutathione conjugates (AFB₁-SG), in both rats and mice; AFB₁-SG was also formed in mouse kidney. Food restriction-induced GST activity assayed in an in vitro system, using [³H]AFB₁-8,9-epoxide and glutathione (GSH) as substrates, was also found when mouse kidney and lung cytosolic fractions were used. Food restriction inhibited the AFB₁-induced DNA double strand breaks in mouse kidney. The reduction of levels of AFB₁-DNA adduct formation in mouse kidney was comparable to the degree of AFB₁-induced DNA strand breakages. The results of this study indicate that the metabolic activation of AFB₁ can be modulated by FR through the alteration of the formation of AFB₁-DNA adducts and AFB₁-SG conjugation. However, species and tissue specificities exist regarding the metabolic activation of AFB₁.