Comparative kinetic studies on aflatoxin B₁ binding to pulmonary and hepatic DNA of rat and hamster receiving the carcinogen intratracheally

Abstract

Several epidemiological studies have discussed the outcome of inhalation of airborne aflatoxins by humans. Metabolism of aflatoxin B1 (AFB1) by lung parenchyma leading to DNA binding is reported here. The tissue distribution pattern of [3H]AFB1 radioactivity revealed the lungs to be the second most important organ after the liver to retain a considerable amount of the radioactivity (66%). The lung indicated a selective activation of AFB1 as it showed only 7.7% binding of [3H]AFB1 to pulmonary DNA. Rats and hamsters were dosed with [3H]AFB1 (2 microCi containing 40 micrograms AFB1/100 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 end of 24 h, the relative AFB1-DNA binding (percentage of peak binding) in hamster lung was 72% while that in rat was 24%. The relative binding in rat lung alveolar macrophages (AMs) was generally higher than that of the hamster. AFB1 binding to hepatic DNA of both the species approached the peak at 1 h after the toxin administration i.t. Under these conditions, binding of AFB1 (or its metabolites translocated to liver) to hepatic DNA of both the species progressively diminished with time in contrast to lung, as revealed by the relative binding values at 12 h for rat and hamster lung, which were 48 and 67%, respectively, while for the rat and hamster liver they were 28 and 24%, respectively. Binding of i.t. administered [3H]AFB1 to rat liver DNA is only marginally higher than that observed with hamster liver, in contrast to the wide difference observed in animals receiving AFB1 intraperitoneally. These results highlight the persistence of AFB1 binding to pulmonary DNA, and the extent of translocated AFB1 binding to hepatic DNA presents an interesting difference from that observed when the toxin was administered through a gastrointestinal route. It is worth concluding that AMs unlike many other xenobiotics, possess specific mixed function oxidase activity to epoxidize AFB1.

Aflatoxin B1-induced micronuclei and cell cycle alterations in lung and bone marrow cells and their modulation byPiper argyrophyllumextract

“…In the present study, a significant binding of AFB 1 to bone marrow cell DNA was observed (Table IV). Earlier studies from our Laboratory have documented AFB 1 binding to pulmonary DNA of rats [16]. AFB 1 adduction to DNA results in the lesion amounting to DNA damage [17], eventually resulting in the DNA strand breaks which in the proliferating cells can result in the micronuclei formation due to segregation of the broken DNA strands during mitotic division.…”

Transformación de la aflatoxina B1 de alimentos, en el cancerígeno humano, aducto AFB1-ADN

“…Los pulmones son el segundo órgano en importancia en retener un 66% de [ 3 H] AFB 1 tritiada. Los macrófagos alveolares poseen una función oxidativa específica para activar la AFB 1 y formar epóxido [66] . La mucosa nasal con las enzimas de la familia P 450 del gen 2A de algunos mamíferos (conejo, rata y humano), los hace susceptibles a la formación del aducto AFB 1 -Gua.…”