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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 Vivo¹

McArdle Laboratory for Cancer Research, University of Wisconsin Medical Center, Madison, Wisconsin 53706

DNA- and ribosomal RNA-bound aflatoxin B₁ 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 B₁ 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 B₁, 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 B₁, adducts also yielded 2,3-dihydro-2,3-dihydroxy-aflatoxin B₁ 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-(N⁵-formyl-2,5,6-triamino-4-oxopyrimidin-N⁵-yl)-3-hydroxy-aflatoxin B₁.

Hydrolysis of the hepatic DNA and ribosomal RNA from rats given injections of [³H]aflatoxin B₁ 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.

¹ This work was supported by Grants CA-07175 and CA-15785 from the National Cancer Institute, USPHS.

² Visiting Professor of Oncology, University of Wisconsin, 1975 to 1976, and recipient of USPHS International Research Fellowship 1-FO5-TWO-2267. Present address: Department of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.

³ To whom requests for reprints should be addressed.

Received 7/ 5/77. Accepted 9/13/77.

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