DOSE-RESPONSE RELATIONSHIPS IN HEPATIC-INJURY PRODUCED BY ALCOHOL ANDCARBON-TETRACHLORIDE

Dose-response relationships were examined for the production of hepati c fibrosis and cirrhosis by combined exposure of male Porton rats to a lcohol and carbon tetrachloride. Alcohol was administered orally in Li eber-DeCarli liquid diet at levels of 75, 150, or 300 kcal/ liter, giv ing mean daily intakes of 2.29, 4.61, and 8.16 g/kg/day, respectively. Carbon tetrachloride was administered by inhalation at concentrations of 10, 20, or 40 ppm, 6 hr/night, 5 nights/week. Liver biopsies were taken at intervals up to a maximum treatment period of 20 weeks. All f our rats that received the high dose of both agents, and 1 of 4 that r eceived the medium alcohol and high carbon tetrachloride treatments, w ere cirrhotic by 10 weeks. Two of the 4 rats that received the low alc ohol and high carbon tetrachloride dose were cirrhotic at 20 weeks. Ci rrhosis was not observed in rats that received the low or medium carbo n tetrachloride dose, but some degree of hepatic fibrosis was observed in all treatment groups. Severity of fibrosis was significantly assoc iated with both dose of alcohol and dose of carbon tetrachloride recei ved. It is concluded that, in the alcohol-carbon tetrachloride rat mod el for chronic liver injury, both alcohol and carbon tetrachloride con tribute to the response in a dose-related manner. Hepatic injury was o bserved even when relatively low doses of these agents are administere d together.