The effect of aflatoxin B1 on RNA synthesis and breakdown in normal and regenerating rat liver

Abstract

The acute effects of a single sublethal dose of aflatoxin B 1 on the metabolism of nuclear RNA in normal and regenerating rat liver were investigated. 1. (1) Two-and-a-half hours after the intraperitoneal injection of aflatoxin B 1 into rats in doses between 1·0 and 1·25 mg/kg of body weight a 30–50% decrease in the incorporation of labelled RNA precursors into rat liver nuclear RNA is observed. Aflatoxin also induces a fall in the RNA/DNA ratio of rat liver nuclei. 2. (2) As judged by the sedimentation profiles of labelled nuclear RNA, obtained by sequential extraction, treatment with aflatoxin impairs the formation of 35 S ribosomal precursor RNA and 28 S RNA. 3. (3) The administration of aflatoxin is also followed by a shift in the 32 P-nucleotide composition of total nuclear RNA extracted after in vivo pulse-labelling with 32 P-orthophosphate to more DNA-like values. The rise in the AMP + UMP/CMP + GMP ratio of 32 P-labelled RNA which follows the application of aflatoxin B 1 is more marked in 24-hr regenerating liver than in normal liver. 4. (4) These in vivo results are paralleled by findings from in vitro experiments: nuclei, isolated from aflatoxin-treated rats display less capacity to synthesize RNA in vitro than control nuclei. This inhibition is maximal when the nuclei are maintained under conditions which are known to favour the formation of an RNA product resembling ribosomal RNA in base composition. 5. (5) Aflatoxin does not induce alterations in the population of rapidly hybridizable RNA species which are detectable by DNA-RNA hybridization experiments. 6. (6) No experimental evidence for an acceleration of the breakdown of preformed hepatic nuclear RNA was found after treatment with aflatoxin B 1 while such an effect could be shown to occur after the administration of actinomycin D. These results which seem to indicate that aflatoxin B 1 exerts a preferential inhibition on the formation of ribosomal RNA are discussed in context with the well-known hepatotoxic and carcinogenic properties of aflatoxin B 1.