Aflatoxin B1 binding to plasma albumin and liver DNA upon chronic administration to rats

Abstract

The hepatocarcinogen aflatoxin B₁ (AFB₁) was administrated to male Wistar rats by oral intubation in either single or repeated doses and the binding to plasma protein and liver DNA determined. Twenty-four hours after a single dose (3.5–200μ/kg AFB₁) a constant ratio was found between levels of alflatoxin bound to plasma protein and that bound to liver DNA. In total 0.98–2.15% of the administrated dose was bound to the plasma protein at this time point. In the chronic study rats received two doses of 0.5μg AFB₁/day and groups of animals were killed on days 2, 3, 7, 14, 21 and 24. Binding of aflatoxin to plasma protein accumulated to a level 3-fold higher than that seen after a single dose. Levels of binding reached a plateau between days 7 and 14 of treatment and then remained stable until the end of the experiment. Binding to DNA also accumulated, 2.5-fold and in parallel to plasma protein, binding reached a plateau between days 7 and 14 of treatment. In both the chronic and acute studies fractionation of the plasma proteins by Sephadex G-200 chromatography showed that all detectable bound aflatoxin was associated with a single peak corresponding to albumin. Thus, a constant ratio was observed, after chronic or single exposure, between the concentration of plasma albumin-bound aflatoxin and that bound to DNA of the liver, the target organ for carcinogenesis by AFB₁. In order to investigate the proposed role of AFB₁ in the aetiology of primary hepato-cellular carcinoma in man it would be of great value to have a method for assessing long-term human exposure at an individual level. The relevance of the observations presented in this paper are discussed in the light of such a requirement.