title: In vitro and in vivo temperature modulation of hepatic metabolism and DNA adduction of aflatoxin B1 in rainbow trout.
abstract: Alterations in membrane lipid composition during temperature acclimation of poikilotherms is hypothesized to compensate for direct effects of temperature on membrane fluidity. Temperature also influences disposition and actions of some xenobiotics. This suggests the potential for complex interactions between temperature and metabolism of chemical carcinogens. Whole livers and hepatic microsomes from rainbow trout acclimated at 18 degrees C have more saturated fatty acids and less mono- and polyunsaturated fatty acids than those from fish acclimated at 10 degrees C. Such changes are consistent with a role for membrane lipid fluidity in temperature compensation. When 10 and 18 degrees C acclimated fish are ip injected with 0.4 mg/kg [3H]aflatoxin B1 (AFB1) at their respective acclimation temperatures, hepatic disposition of AFB1, DNA adduction, and biliary metabolites are similar. An acute shift of 18 degrees C acclimated trout to 14 degrees C reduces [3H]AFB-DNA adduct formation, while [3H]AFB1 adduction after acute shift of 10 degrees C acclimated fish to 14 degrees C is no different than in non-shifted fish. Hepatic microsomes isolated from 10 or 18 degrees C acclimated trout, incubated with 10 microM [3H]AFB1 and calf thymus DNA between 6 and 22 degrees C exhibit no differences in the "break points" of Arrhenius plots (16 degrees C in both groups). There is, however, more in vitro DNA adduction of [3H]AFB1 by microsomes from 18 degrees C acclimated fish, a difference abolished by 0.5 mM alpha-naphthoflavone (ANF). These results suggest that temperature acclimation of trout differentially modifies activities of cytochrome P-450 isozymes. When assayed at respective acclimation temperatures, hepatic cytosol from 18 degrees C fish produces more aflatoxicol, a detoxication product of AFB1, than cytosol from 10 degree C fish. Therefore, this soluble enzyme does not exhibit ideal temperature compensation. Such temperature-induced differences in microsomal cytochrome P-450 isozymes and cytosolic dehydrogenase partially explain temperature-modulated AFB1 genotoxicity.
authors.affiliation: Oak Creek Laboratory of Biology, Oregon State University, Corvallis 97331, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Carpenter
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: el Zahr
authors.forename: D P
authors.initials: DP
authors.lastname: Selivonchick
authors.forename: D E
authors.initials: DE
authors.lastname: Brock
authors.forename: L R
authors.initials: LR
authors.lastname: Curtis
mesh_terms: D000064:Acclimatization; D016604:Aflatoxin B1 / Q000032:analysis* / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis*; D005227:Fatty Acids / Q000032:analysis; D066298:In Vitro Techniques; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D013696:Temperature
chemical_list: D018736:DNA Adducts; D005227:Fatty Acids; C072611:aflatoxin B1-DNA adduct; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D010088:Oxidoreductases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase