US EPA

4120483 

Journal Article 

Aflatoxin B1: Binding To DNA In Vitro And Alteration Of RNA Metabolism In Vivo 

Sporn, MB; Dingman, CW; Phelps, HL; Wogan, GN 

1966 

1 

Science
ISSN: 0036-8075
EISSN: 1095-9203 

NIOSH/00157067 

151 

3717 

1539-1541 

Aflatoxin-B1 (1162658) binding to DNA in-vitro and the effects on RNA metabolism in-vivo were examined in rats. For the RNA study, three groups of animals were used. Group 1 was injected with 0.1 milliliter (ml) of dimethylsulfoxide (67685) (DMSO) and groups 2 and 3 with 5 milligrams per kilogram (mg/kg) aflatoxin-B1 in 0.1ml DMSO. All animals were injected with 80 microCuries of tritiated cytidine (65463). Groups 1 and 2 were sacrificed at 70 minutes and group 3 at 17 hours after exposure. Ratios of nuclear RNA to DNA were determined and radioactivity in nuclear RNA was assayed. Equilibrium dialysis was used to measure binding of aflatoxin-B1 to DNA. Aflatoxin-B1 solutions of 33 nanomoles/ml in a 0.01 molar solution of potassium-phosphate were dialyzed for 5 days at 2 degrees-C against 15 volumes of 0.01 molar solution potassium-phosphate. Aflatoxin-B1 was found to bind to DNA in-vitro. In-vivo, it rapidly inhibited incorporation of tritiated cytidine into rat liver nuclear RNA and lowered the ratio of nuclear RNA to DNA. A shift in the absorption spectrum occurred when aflatoxin-B1 was bound to DNA. Administration of the toxin at 5mg/kg caused virtually complete inhibition of enzyme inducibility, which persisted for as long as 10 days after administration. The authors conclude that the binding of aflatoxin-B1 to DNA may be of prime importance in the mechanism of action of this compound. The binding of the substance is a crucial aspect of its toxic and carcinogenic properties.