Changes in phase I and phase II biotransformation with age in male Fischer 344 rat colon: relationship to colon carcinogenesis.
Using male Fischer 344 rats classified as young (2-4 months), middle aged (12-14 months), and old (22-25 months), the activities of several Phase I and Phase II biotransformation pathways in the large intestine were investigated, including benzo[a]pyrene hydroxylase (BPOH), alcohol dehydrogenase (ADH), glutathione S-transferase (GST), glutathione peroxidase (GSH-PX), beta-glucuronidase (BG), and microsomal and nuclear glucuronyltransferase (UDPGT). Levels of oxidized (GSSG) and reduced (GSH) glutathione and uridine 5'-diphosphoglucuronic acid (UDPGA) were also measured. BPOH increased 33% in old rats, while ADH and BG activity remained unchanged with age. Nuclear UDPGT remained unchanged with age, whereas form I of GSH-PX declined slightly in old rats. GST, microsomal UDPGT, and form II of GSH-PX declined by 38, 37 and 44%, respectively, in old rats. The decrease in GST and microsomal UDPGT was also significant in middle aged rats. Levels of colonic GSH, GSSG and UDPGA were found to be unchanged with age. These in vitro data suggest the possibility that if reactive intermediates are generated to the same extent in old rats as in young rats, decreased detoxification mechanisms in the old rat may increase susceptibility of the colon to actions of chemical carcinogens.
D000375:Aging / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D002273:Carcinogens / Q000493:pharmacokinetics*; D003106:Colon / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008658:Inactivation, Metabolic; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D000426:Alcohol Dehydrogenase; D005979:Glutathione Peroxidase; D001579:Benzopyrene Hydroxylase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase