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Repair of DNA in Human Cells after Treatment with Activated Aflatoxin B₁¹

Department of Biological Sciences, Stanford University, Stanford, California 94305

Repair replication was examined in cultured human cells exposed to the hepatocarcinogen aflatoxin B₁ using the combined bromodeoxyuridine density label and radioisotopic label method. Semiconservative DNA synthesis was strongly inhibited, and the repair replication mode was stimulated in diploid fibroblasts (WI38) and in their SV40 transformants (VA13) only when exposure to aflatoxin B₁ was in the presence of an activating system containing rat liver microsomal enzymes. The maximum amount of repair synthesis was about 20% of that obtained after saturating doses of ultraviolet light (UV). The time course of repair synthesis was similar to that seen after UV, and most of the synthesis was in 30- to 50-nucleotide "short patches." A line of SV40-transformed xeroderma pigmentosum cells (Group A) deficient in repair after exposure to UV was similarly deficient in repair replication after aflatoxin treatment.

Treatment with aflatoxin resulted in a 25 to 45% inhibition of UV-induced repair replication, suggesting that in addition to producing lesions in DNA, which are substrates for the excision repair system, the toxin also inhibits excision repair.

CsCl gradients of DNA treated in vitro with activated aflatoxin demonstrated binding of the drug to DNA. Alkaline sucrose gradient sedimentation gave no indication that single-strand breaks or alkali labile bonds were introduced into DNA by treatment of cells with activated aflatoxin.

¹ This work was supported by Grant NP-161 from the American Cancer Society and Grant GM 09901 from the National Institute of General Medical Sciences. A preliminary account of some of this work was presented at the Second International Workshop on DNA Repair Mechanisms in Mammalian Cells, May 1976, Noordwijkerhout, The Netherlands.

² Recipient of a Research Training Fellowship from the International Agency for Research on Cancer, Lyon, France. Present Address: Institut de Recherches Scientifiques sur le Cancer, Boite Postale 8, 94800 Villejuif, France.

Received 12/ 3/76. Accepted 3/14/77.

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