IN-VIVO BIOTRANSFORMATION OF AFLATOXIN-B1 AND ITS INTERACTION WITH CELLULAR MACROMOLECULES IN NEONATAL RATS

In this study, the ability of neonatal rat liver to metabolise [H-3]af latoxin B1 (AFB1) was compared to that of the adult animal. In order t o make this comparison, neonatal and young adult rats were killed 2, 6 , 12 and 24 h after injection with a single i.p. dose of AFB1. The rat e of AFB1 adduct formation to nuclear DNA and protein was measured in hepatic and pulmonary tissues. The results demonstrated that AFB1 was epoxidized more rapidly by the adult's liver and lungs 2 h after the t oxin administration, compared with those of the neonatal's (adult 30 p mol and neonatal 12 pmol AFB1 bound/mg DNA). However, these difference s were more pronounced in hepatic than in pulmonary tissues. The same differences between AFB1-DNA adducts were also observed at different t ime points. These changes are certainly related to the level of hepati c cytochrome P-450. The delayed cytochrome P-450-dependent AFB1 activa tion in neonatal's liver provides time enough for de-epoxidation of sl owly generated epoxide. The rate of AFB1-epoxide formation at this age was consistent with the activity of phase II metabolism of AFB1 (glut athione conjugation). In addition, the hydrolysis of AFB1-DNA adducts at a relatively higher rate by neonatal's liver may also contribute to the quick removal of the adducts. In spite of the aforementioned evid ence which shows the capability of neonatal liver to handle AFB1, the fate of large amounts of free (non-metabolised) AFB1 deposited in neon atal's liver is not well understood.