Repair of DNA in human cells after treatment with activated aflatoxin B1.
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 (W138) 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. CsC1 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.
D000348:Aflatoxins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013539:Simian virus 40; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000378:metabolism
D000348:Aflatoxins; D004277:DNA, Single-Stranded; D004247:DNA