COMPARATIVE KINETIC-STUDIES ON AFLATOXIN B-1 BINDING TO PULMONARY ANDHEPATIC DNA OF RAT AND HAMSTER RECEIVING THE CARCINOGEN INTRATRACHEALLY

Several epidemiological studies have discussed the outcome of inhalati on of airborne aflatoxins by humans. Metabolism of aflatoxin B-1 (AFB( 1)) by lung parenchyma leading to DNA binding is reported here. The ti ssue distribution pattern of [H-3]AFB(1) radioactivity revealed the lu ngs to be the second most important organ after the liver to retain a considerable amount of the radioactivity (66%). The lung indicated a s elective activation of AFB(1) as it showed only 7.7% binding of [H-3]A FB(1) to pulmonary DNA. Rats and hamsters were dosed with [H-3]AFB(1) (2 mu Ci containing 40 mu g AFB(1)/100 g body wt.) intratracheally (i. t.) and sacrificed at different intervals after toxin treatment. Peak binding occurred at 0.5, 1, and 2 h in case of hamster lung, rat lung, and alveolar macrophages of both the species, respectively. At the en d of 24 h, the relative AFB(1)-DNA binding (percentage of peak binding ) in hamster lung was 72% while that in rat was 24%. The relative bind ing in rat lung alveolar macrophages (AMs) was generally higher than t hat of the hamster. AFB(1) binding to hepatic DNA of both the species approached the peak at 1 h after the toxin administration i.t. Under t hese conditions, binding of AFB(1) (or its metabolites translocated to liver) to hepatic DNA of both the species progressively diminished wi th time in contrast to lung, as revealed by the relative binding value s at 12 h for rat and hamster lung, which were 48 and 67%, respectivel y, while for the rat and hamster liver they were 28 and 24%, respectiv ely. Binding of i.t. administered [H-3]AFB(1) to rat liver DNA is only marginally higher than that observed with hamster liver, in contrast to the wide difference observed in animals receiving AFB(1) intraperit oneally. These results highlight the persistence of AFB(1) binding to pulmonary DNA, and the extent of translocated AFB(1) binding to hepati c DNA presents an interesting difference from that observed when the t oxin was administered through a gastrointestinal route. It is worth co ncluding that AMs unlike many other xenobiotics, possess specific mixe d function oxidase activity to epoxidize AFB(1). (C) 1993 Wiley-Liss, Inc.