PMID- 11790349 OWN - NLM STAT- MEDLINE DCOM- 20020301 LR - 20191210 IS - 1532-0456 (Print) IS - 1532-0456 (Linking) VI - 125 IP - 3 DP - 2000 Mar TI - 3,3',4,4'-Tetrachlorobiphenyl oxidation in fish, bird and reptile species: relationship to cytochrome P450 1A inactivation and reactive oxygen production. PG - 273-86 AB - Previously we showed that the polychlorinated biphenyl 3,3',4,4'-tetrachlorobiphenyl (TCB) caused a release of reactive oxygen species (ROS) from cytochrome P450 1A (CYP1A) of the fish scup (Stenotomus chrysops), and from rat and human CYP1A1. This was linked to a TCB- and NADPH-dependent oxidative inactivation of the enzyme, which in scup and rat was inversely related to the rates of TCB oxidation. We examined the relationship between rates of TCB oxidation, CYP1A inactivation and ROS production in liver microsomes from additional vertebrate species, including skate (Raja erinacea), eel (Anguilla rostrata), killifish (Fundulus heteroclitus), winter flounder (Pleuronectes americanus), chicken (Gallus domesticus), cormorant (Phalacrocorax auritus), gull (Larus argentatus), and turtle (Chrysemys picta picta). TCB oxidation rates were induced in all fish and birds treated with aryl hydrocarbon receptor agonists. Induced rates of TCB oxidation were <1 pmol/min/mg microsomal protein in all fish, and 6-14 pmol/min/mg in the birds. In all species but one, TCB oxidation rates correlated positively with EROD rates, indicating likely involvement of CYP1A in TCB oxidation. Incubation of liver microsomes of most species with TCB+NADPH resulted in an immediate (TCB-dependent) inhibition of EROD, and a progressive loss of EROD capacity, indicating an oxidative inactivation of CYP1A like that in scup. NADPH stimulated production of ROS (H(2)O(2) and/or O(2)(-*)) by liver microsomes, slightly in some species (eel) and greatly in others (chicken, turtle). Among the birds and the fish, NADPH-stimulated ROS production correlated positively with EROD activity. TCB caused a significant stimulation of ROS production by liver microsomes of flounder, killifish, cormorant and gull, as well as scup. The stimulation of CYP1A inactivation and ROS generation indicates an uncoupling of CYP1A by TCB in many species, and when compared between species, the rates of CYP1A inactivation correlated inversely with rates of TCB oxidation. Some feature(s) of binding/active site topology may hinder TCB oxidation, enhancing the likelihood for attack of an oxidizing species in the active site. FAU - Schlezinger, J J AU - Schlezinger JJ AD - Biology Department, Redfield 342, MS 32, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA. FAU - Keller, J AU - Keller J FAU - Verbrugge, L A AU - Verbrugge LA FAU - Stegeman, J J AU - Stegeman JJ LA - eng GR - P42-ES07381/ES/NIEHS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Comp Biochem Physiol C Toxicol Pharmacol JT - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP JID - 100959500 RN - 0 (Reactive Oxygen Species) RN - 0 (Receptors, Aryl Hydrocarbon) RN - 1364PS73AF (Acetone) RN - 53-59-8 (NADP) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) RN - Y2I6546TMI (3,4,3',4'-tetrachlorobiphenyl) SB - IM MH - Acetone/pharmacology MH - Anguilla MH - Animals MH - Birds MH - Chickens MH - Cytochrome P-450 CYP1A1/drug effects/*metabolism MH - Female MH - Flounder MH - Fundulidae MH - Microsomes, Liver/drug effects/enzymology MH - NADP/pharmacology MH - Oxidation-Reduction MH - Polychlorinated Biphenyls/*metabolism MH - Reactive Oxygen Species/*metabolism MH - Receptors, Aryl Hydrocarbon/agonists/drug effects MH - Skates, Fish MH - Species Specificity MH - Turtles EDAT- 2002/01/16 10:00 MHDA- 2002/03/02 10:01 CRDT- 2002/01/16 10:00 PHST- 2002/01/16 10:00 [pubmed] PHST- 2002/03/02 10:01 [medline] PHST- 2002/01/16 10:00 [entrez] AID - S0742841399001127 [pii] AID - 10.1016/s0742-8413(99)00112-7 [doi] PST - ppublish SO - Comp Biochem Physiol C Toxicol Pharmacol. 2000 Mar;125(3):273-86. doi: 10.1016/s0742-8413(99)00112-7.