CHEMOPREVENTIVE EFFECTS OF DITHIOCARBAMATES ON AFLATOXIN B-1 METABOLISM AND FORMATION OF AFB(1) ADDUCTS WITH GLUTATHIONE

Several agents with anticarcinogenic potential such as diethyldithioca rbamate (DDTC), lactose-DDTC, proline-dithiocarbamate (PDTC), its dime r proline-thiurandisulfide (PTDS) and 4-carboxy-piperazine-TDS (4-pip- TDS) were investigated for their influence on the metabolism and the d etoxication of aflatoxin B-1 (AFB(1)) in vitro and in vivo. Aflatoxins are a group of mycotoxins produced by aspergillus species and are amo ng the most important risk factors for hepatocellular carcinoma in cer tain areas of the world. AFB(1) metabolism measured by the formation o f tris-diol adducts showed that the thiuramdisulfides 4-carboxy-pipera zine-TDS and PTDS were better inhibitors in vitro than the correspondi ng dithiocarbamates. Ex vivo studies in rats showed that dithiocarbama tes (DTCs) including sugar linked lactose-DDTC decreased the formation of tris-diol adducts. Among the dithiocarbamates administered DDTC sh owed a 40 % inhibition whereas the other compounds showed only margina l effects. In vivo experiments on the formation of glutathione-adducts derived from AFB(1)-endo- and exo-epoxides showed that lactose-DDTC e nhanced the formation of AFB(1)-GSH adducts, whereas PDTC, 4-pip-TDS, PTDS and DDTC displayed inhibitory effects. We conclude that DTCs may be promising agents in the chemoprevention of liver carcinogenesis cau sed by AFB(1).