Comparison of aflatoxin B1-DNA binding and glutathione conjugate formation by liver preparations from rats of different ages.
The capability of the newborn rat liver to detoxify aflatoxin B1 (AFB1), a potent hepatocarcinogen is not well understood. Our present results show that immature rats are deficient in the hepatic key factors involved in biotransformation of AFB1. The activities of cytosolic glutathione S-transferases and microsomal cytochrome P-450 along with cellular glutathione (GSH) content show postnatal developmental changes. The ability of hepatic subcellular preparation from newborn rats to convert AFB1 to its reactive epoxide form, is reported for the first time in this communication. Epoxidation of [3H]AFB1 in the presence of liver microsomes from different age-groups as measured by its adduct formation to calf thymus DNA in vitro shows that newborn rats are capable of catalyzing only minimal AFB1-DNA binding compared with that of adults. Addition of cytosolic fraction of various age groups to the system suggests that young rats are less efficient in modulating the binding as compared with adults. The amount of AFB1-GSH conjugate formed is also significantly higher when adult GSH S-transferase is involved in the system. These observations show that immature liver is less efficient than a mature organ in handling a chemical carcinogen and the metabolism of AFB1 by neonatal liver differs from that in the adult.
Behroozikha
M
M
Department of Biochemistry, Faculty of Medical Sciences, Tarbiat Modaress University, Tehran, Iran.
Saidee
M
M
Allameh
A
A
D016604:Aflatoxin B1 / Q000378:metabolism* / Q000493:pharmacokinetics; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism
D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D005982:Glutathione Transferase; D005978:Glutathione