Chloroform bioactivation by microsomes from colonic and ileal mucosa of rat and man.
The cytochrome P-450 system present in colonic and small-intestinal mucosal microsomes from control and beta-naphthoflavone pretreated rats is not able to catalyze the biotransformation of chloroform either oxidatively or reductively. Anoxic incubations of 14CHCl3 with mucosal microsomes obtained from human colon and ileum biopsies resulted in significant levels of covalent binding to lipids but not to protein; no covalent binding was measured after room-air-equilibrated incubations. The bioactivation of CHCl3 by human colonic mucosal microsomes can therefore occur in conditions which may be representative of the physiologically low oxygenation of the outer layers of this tissue. These results support the possibility of an association between colonic cancer and exposure to CHCl3, claimed in some epidemiological studies, but not evident from studies of laboratory animals.
Testai
E
E
Department of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Rome, Italy.
Keizer
J
J
Pacifici
G M
GM
Vittozzi
L
L
D000818:Animals; D001711:Biotransformation; D002725:Chloroform / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000201:enzymology*; D007413:Intestinal Mucosa / Q000201:enzymology*; D050356:Lipid Metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D011506:Proteins; D002725:Chloroform; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases