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1992 Fiscal Year Final Research Report Summary

Immunochemical assessment of the influencing factors on the metabolism of organic solvents

Research Project

Project/Area Number 02807059
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Hygiene
Research InstitutionShinshu University School of Medicine

Principal Investigator

NASU Tamie  Shinshu Univ. Sch. Med. Lecturer, 医学部, 講師 (10020794)

Project Period (FY) 1990 – 1992
KeywordsCytochrome P450 / Monoclonal antibody / metabolism / toxicity / organic solvents / ethanol / nutritional status / age
Research Abstract

Characterization of cytochrome P450 isozyme responsible for the metabolism of organic solvents and the factors influencing the metabolism were investigated in rats using monoclonal antibody to cytochrome P450. CYP2B1/2, 2E1 and 2C11/6 were involved in toluene side-chain reaction; CYP1A1/2, 2B1/2 and 2C11/6 in o-cresol formation from toluene; CYP1A1/2, 2B1/2, 2E1 and 2C11/6 in p-cresol formation from toluene. These four isozymes were also involved in benzene, styrene and trichloroethylene (TRI) metabolism. CYP2C11/6 was a major isozyme responsible for toluene and styrene metabolism, whereas CYP2E1 in the metabolism of benzene and TRI. In general, CYP2E1 acted the metabolism of organic solvents as a lower Km isozyme than CYP2C11/6. CYP2E1 was induced with ethanol consumption, the intake of low-carbohydrate diet. fasting and diabetic status, whereas decreased with aging and pregnancy. The level of CYP2C11/6 increased with aging, and predominantly expressed in males at adult age. This isozyme, however, decreased with pregnancy and diabetic status. Species differences were found in the metabolism of benzene, toluene, styrene and TRI between rat and mouse. The metabolic rates of benzene and TRI were always higher in adult male mouse than in adult male rat. The rates of toluene and styrene were also higher in mouse than in rat at low substrate concentrations, but the result was reversed at the high concentration. Mouse had much more CYP2E1 than rats, whereas CYP2C11/6 predominantly expressed in rat, suggesting that one reason of species difference in the metabolism of organic solvents between rat and mouse depends on the difference in the distribution of P450 isozymes. CYP2E1 was involved in carbon tetrachloride and chloroform hepatotoxicity at the low level. In conclusion, since cytochrome P450 shows substrate specificity for organic solvents, any hazard from the exposure of organic solvents may depend on the P450 isozyme profile in the target organ.

  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Nakajima T et al: "Immunochemical characterization of cytochrom P-450 isozymes responsible for benzene oxidation in rat liver" Carcinogenesis. 9. 1713-1717 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "Three forms of trichloroethylene-metabolizing enzymes in rat liver by ethanol,phenobarbital and 3-methyl-choranthrene" Toxicol Appl Pharmacol. 102. 546-552 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] NakaJima T et al: "Monoclonal antibody-directed characterization of benzene ethoxyresorufin and pentoxyresorufin metabolism in rat liver microsomes" Biochem Pharmacol. 40. 1255-1261 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "Immunochemical detection of cytochrome P450isozymes induced in rat liver by n-hexane,2-hexanone and acetonyl acetone." Arch Toxicol. 65:. 542-547 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "Monoclonal antibody-directed characterization of cytochrome P450 isozymes responsible for toluene metabolism in rat liver" Biochem Pharmacol. 41. 395-404 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Elovaara E et al: "Metabolism of inhaled styrene in acetone-,phenobarbital- and 3-methylcholanthrene-pretreated rats:stimulation and stereochemical effects by induction of cytochrome・・・" Xenobiotica. 21. 651-661 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okino T,Nakajima T et al: "Morphological and biochemical analyses of trichloroethylene hepatotoxicity:differneces in ethanol-and phenobarbital induced rats" Toxicol Appl Pharmacol. 103. 379-389 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikatsu H et al: "Ethanol and food deprivation induced enhancement of hepatotoxicity in rats given carbon tetrachloride at low concentration" Br J Ind Med. 48. 636-642 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中島民江: "有機溶剤の代謝毒性とチトクロームP450" 信州医誌. 39. 199-212 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "Enhancement of ethanol-induced lipid peroxidation in rat liver by lowered carbohydrate intake" Biochem Pharmacol. 43. 245-250 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "A comparative study on the contribution of cytochrome P450 isozymes to metabolism of benzene,toluene and trichloroethylene in rat liver" Biochem Pharmacol. 43. 251-257 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wang RS,Nakajima T: "Effects of ethanol and phenobarbital treatments on the pharmacokinetics of toluene in rat" Br J Ind Med. 49. 104-112 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "Sex-,age,and pregnancy-induced changes in the metabolism of toluene and trichloroethylene in rat liver in relation to the regulation of P450IIE1 and P450IIC11/content" J Pharmacol Exp Ther. 261. 869-874 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikatsu H,Nakajima T: "Hepatotoxic interaction between carbon tetrachloride and chloroform in ethanol-treated rsts" Arch Toxicol. 66. 580-586 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "Cytochrome P450-related differences between rats and mice in the metabolism of benzene,toluene and trichloroethylene in liver microsomes" Biochem Pharmacol. (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wang RS,Nakajima T: "Kinetic studies on toluene metabolism ethanol- and phenobarbital-induced rat liver microsomes in vitro" Arch Toxicol. 65. 39-44 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "International Symposium on Biological Monitoring" Springer International, (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima T et al: "Immunochemical characterization of cytochrome P-450 isozymes responsible for benzene oxidation in rat liver." Carcinogenesis. 9. 1713-1717 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T et al: "Three forms of trichloroethylene-metabolizing enzymes in rat liver by ethanol. phenobarbital and 3-methylcholanthrene." Toxicol Appl Pharmacol. 102. 546-552 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T et al: "Monoclonal antibody-directed characterization of benzene,ethoxyresorufin and pentoxyresorufin metabolism in rat liver microsomes." Biochem Pharmacol. 40. 1255-1261 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T et al: "Immunochemical detection of cytochrome P450 isozymes induced in rat liver by n-hexane, 2-hexanone and acetonyl acetone." Arch Toxicol. 65. 542-547 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T et al: "Monoclonal antibody-directed characterization of cytochrome P450 isozymes responsible for toluene metabolism in rat liver." Biochem Pharmacol. 41. 395-404 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Elovaara E et al: "Metabolism of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-pretreated rats: stimulation and stereochemical effects by induction of cytochromes P450IIE1. P450IIB and P450IA." Xenobiotica. 21. 651-661 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okino T et al: "Morphological and biochemical analyses of trichloroethylene hepatotoxicity: differences in ethanol- and phenobarbital-pretreated rats." Toxicol Appl Pharmacol. 108. 379-389 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikatsu H, et al: "Ethanol and food deprivation induced enhancement of hepatotoxicity in rats given carbon tetrachloride at low concentration." Br J Ind Med. 48. 636-642 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T: "Cytochrome P450 in relation to the metabolism and toxicity of organic solvents." Shinshu Med J. 39. 199-212 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wang RS and Nakajima T: "Kinetic studies on toluene metabolism in ethanol- and phenobarbital-induced rat liver microsomesm in vitro." Arch Toxicol. 65. 39-44 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T et al: "Enhancement of ethanol-induced lipid peroxidation in rat liver by lowered carbohydrate intake." Biochem Pharmacol. 43. 245-250 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T: "A comparative study on the contribution of cytochrome P450 isozymes to metabolism of benzene, toluene and trichloroethylene in rat liver." Biochem Pharmacol. 43. 251-257 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wang RS and Nakajima T: "Effects of ethanol and phenobarbital treatments on the pharmacokinetics of toluene in rats." Br J Ind Med. 49. 104-112 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T et al: "Sex-, age- and pregnancy-induced changes in the metabolism of toluene and trichloroethylene in rat liver in relation to the regulation of cytochrome P450IIE1 and P450IIC11 content." J Pharmacol Exp Then. 261. 869-874 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikatsu H and Nakajima T: "Hepatotoxic interaction between carbon tetrachloride and chloroform in ethanol treated rats." Arch Toxicol. 66. 580-586 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima T: "Cytochrome P450-related differences between rats and mice in the metabolism of benzene, toluene and trichloroethylene in liver microsomes." Biochem Pharmacol. (1993)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1994-03-24  

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