2,3-Dihydro-2-(guan-7-yl)-3-hydroxy-aflatoxin B1, a major acid hydrolysis product of aflatoxin B1-DNA or -ribosomal RNA adducts formed in hepatic microsome-mediated reactions and in rat liver in vivo.

Abstract

Summary DNA- and ribosomal RNA-bound aflatoxin B 1 adducts obtained from salmon sperm DNA and rat liver ribosomal RNA with fortified rat and hamster liver microsomes were hydrolyzed with weak acid to yield 2,3-dihydro-2-(guan-7-yl)-3-hydroxy-aflatoxin B 1 as the major product. This product was characterized on the basis of its nuclear magnetic resonance, ultraviolet, and infrared spectra; its hydrolysis to guanine, 2,3-dihydro-2,3-dihydroxy-aflatoxin B 1 , and acid degradation products of the latter; its deamination to a product that yielded xanthine on hydrolysis; and the susceptibility of its nucleic acid precursors to hydrolysis in weak alkali. Acid hydrolysis of the nucleic acid-aflatoxin B 1 , adducts also yielded 2,3-dihydro-2,3-dihydroxy-aflatoxin B 1 and two minor products, the amounts of which were greatly increased if the nucleic acid adducts were previously exposed to weak alkali. One of the latter compounds was tentatively identified as 2,3-dihydro-2-( N 5 -formyl-2,5,6-triamino-4-oxopyrimidin- N 5 -yl)-3-hydroxy-aflatoxin B 1 . Hydrolysis of the hepatic DNA and ribosomal RNA from rats given injections of [ 3 H]aflatoxin B 1 liberated tritiated products that cochromatographed on high-performance liquid chromatography in four solvent systems with the products obtained on hydrolysis of the adducts formed in vitro . The identification of the major product from the adducts formed in vivo with that from the adducts formed in vitro was further shown by the chromatographic identities of the derivatives formed on acetylation, deamination, and acid hydrolysis of the major product from each of the two sources.