title: Food restriction reduces aflatoxin B1 (AFB1)-DNA adduct formation, AFB1-glutathione conjugation, and DNA damage in AFB1-treated male F344 rats and B6C3F1 mice.
abstract: 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.
authors.affiliation: Division of Nutritional Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Chou
authors.forename: W
authors.initials: W
authors.lastname: Chen
mesh_terms: D016604:Aflatoxin B1 / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D001835:Body Weight; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D005508:Food Deprivation / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; D016604:Aflatoxin B1; D005978:Glutathione