ABSTRACT
To test the hypothesis that occupational exposure to chemical agents-particularly organic solvents in certain industries-may cause primary liver cancer (PLC), a nested case-control study of PLC cases from the Danish Cancer Registry and an age- and sex-stratified random sample of controls from the Central Population Register in Denmark were linked with files of a national supplementary pension fund. Employment histories since April 1964 were obtained for 973 cases histologically classified as hepatocellular carcinoma, cholangiocarcinoma, or combined hepatocellular and cholangiocarcinoma and 15,348 controls. Men from 35 different industrial branches, women from 7 branches, and both men and women from 3 branches had an excess risk of PLC, with an odds ratio of (OR) > 1.0; 29 branches had an OR of liver cancer in excess of 3.0. Women from bookprinting and offset printing industries had an OR above 10. Only male farmers had an OR below unity (0.41). Employees from breweries, restaurants, hotels, motels, and distilleries had an increased OR of both PLC and esophageal cancer.
Subject(s)
Liver Neoplasms/epidemiology , Occupational Diseases/epidemiology , Occupational Exposure/adverse effects , Solvents/adverse effects , Aged , Bile Duct Neoplasms/epidemiology , Bile Duct Neoplasms/etiology , Bile Ducts, Intrahepatic/pathology , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Case-Control Studies , Cholangiocarcinoma/epidemiology , Cholangiocarcinoma/etiology , Confidence Intervals , Denmark/epidemiology , Female , Humans , Liver Neoplasms/etiology , Male , Middle Aged , Occupational Diseases/etiology , Odds Ratio , Risk FactorsSubject(s)
Antipyrine/metabolism , Environmental Exposure , Liver/metabolism , Menstruation , Adult , Age Factors , Alcohol Drinking , Feeding Behavior , Female , Humans , Physical Exertion , Sex Factors , SmokingABSTRACT
The effect of cimetidine, antipyrine and phenobarbitone on the pharmacokinetics of intravenous metronidazole and oral antipyrine has been examined in 7 healthy volunteers. The administration of cimetidine for 24 h before and throughout the sampling period failed to alter the total clearance of metronidazole or the rate of formation of the hydroxy metabolite, whereas the total and partial clearances of antipyrine were decreased 0.74 and 0.6-0.7-fold, respectively. Seven days of phenobarbitone or antipyrine administration increased the total clearance of metronidazole 1.51- and 1.86-fold, respectively, and the total antipyrine clearance was 1.22 or 1.46-fold increased, respectively. The rate of metronidazole hydroxylation was significantly enhanced by both enzyme inducers. The partial clearance of antipyrine to the normetabolite was significantly increased by both inducers, whereas the rate of 4-hydroxylation was significantly increased only by prior antipyrine administration. The results indicate that the hydroxylation of metronidazole is not inhibited by cimetidine, but that it is inducible by phenobarbitone or antipyrine. It is suggested that metronidazole and antipyrine are metabolized by different enzymatic pathways.
