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. 1976 Oct;73(10):3723–3725. doi: 10.1073/pnas.73.10.3723

Aryl 4-monooxygenase and cytochrome P-450 in the aorta: possible role in atherosclerosis.

M R Juchau, J A Bond, E P Benditt
PMCID: PMC431191  PMID: 824648

Abstract

Aryl 4-monooxygenase [aniline, reduced-flavoprotein:oxygen oxidoreductase (4-hydroxylating); EC 1.14.14.1] activity was searched for and found in homogenates of aorta walls from rabbits, rhesus monkeys, and humans. Specific activities were comparable to activities observed in several other extrahepatic tissues of rabbits and monkeys and in epidermal tissues from mice, but were one to two orders of magnitude lower than those observed in corresponding preparations of hepatic tissues. Cytochrome P-450 also could be detected in low concentrations in microsomal fractions of aortic wall homogenates. The monooxygenase activity found in the aorta could play a significant role in the etiology and pathogenesis of atherosclerosis in humans by catalyzing the conversion of environmental promutagens to mutagenic initiators and/or cytotoxic factors, thus leading to development of benign, smooth muscle tumors of the inner lining of artery walls.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benditt E. P., Benditt J. M. Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1753–1756. doi: 10.1073/pnas.70.6.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benditt E. P. Evidence for a monoclonal origin of human atherosclerotic plaques and some implications. Circulation. 1974 Oct;50(4):650–652. doi: 10.1161/01.cir.50.4.650. [DOI] [PubMed] [Google Scholar]
  3. Biermann E. L., Albers J. J. Lipoprotein uptake and degradation of human arterial smooth muscle cells in tissue culture. Ann N Y Acad Sci. 1976;275:199–203. doi: 10.1111/j.1749-6632.1976.tb43353.x. [DOI] [PubMed] [Google Scholar]
  4. Feldmann R. J., Maibach H. I. Absorption of some organic compounds through the skin in man. J Invest Dermatol. 1970 May;54(5):399–404. doi: 10.1111/1523-1747.ep12259184. [DOI] [PubMed] [Google Scholar]
  5. Gelboin H. V., Huberman E., Sachs L. Enzymatic hydroxylation of benzopyrene and its relationship to cytotoxicity. Proc Natl Acad Sci U S A. 1969 Dec;64(4):1188–1194. doi: 10.1073/pnas.64.4.1188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gelboin H. V., Kinoshita N., Wiebel F. J. Microsomal hydroxylases: induction and role in polycyclic hydrocarbon carcinogenesis and toxicity. Fed Proc. 1972 Jul-Aug;31(4):1298–1309. [PubMed] [Google Scholar]
  7. Greim H. Synthesesteigerung und Abbauhemmung bei der Vermehrung der mikrosomalen Cytochrome P-450 und b-5 durch Phenobarbital. Naunyn Schmiedebergs Arch Pharmakol. 1970;266(3):260–275. [PubMed] [Google Scholar]
  8. Heidelberger C. Chemical carcinogenesis. Annu Rev Biochem. 1975;44:79–121. doi: 10.1146/annurev.bi.44.070175.000455. [DOI] [PubMed] [Google Scholar]
  9. Jerina D. M., Daly J. W. Arene oxides: a new aspect of drug metabolism. Science. 1974 Aug 16;185(4151):573–582. doi: 10.1126/science.185.4151.573. [DOI] [PubMed] [Google Scholar]
  10. Juchau M. R., Pedersen M. G. Drug biotransformation reactions in the human fetal adrenal gland. Life Sci II. 1973 Mar 8;12(5):193–204. doi: 10.1016/0024-3205(73)90347-0. [DOI] [PubMed] [Google Scholar]
  11. Juchau M. R., Zachariah P. K., Colson J., Symms K. G., Krasner J., Yaffe S. J. Studies on human placental carbon monoxide-binding cytochromes. Drug Metab Dispos. 1974 Jan-Feb;2(1):79–86. [PubMed] [Google Scholar]
  12. Kinoshita N., Shears B., Gelboin H. V. K-region and non-K-region metabolism of benzo(a)pyrene by rat liver microsomes. Cancer Res. 1973 Aug;33(8):1937–1944. [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Linder D., Gartler S. M. Glucose-6-phosphate dehydrogenase mosaicism: utilization as a cell marker in the study of leiomyomas. Science. 1965 Oct 1;150(3692):67–69. doi: 10.1126/science.150.3692.67. [DOI] [PubMed] [Google Scholar]
  15. Moss N. S., Benditt E. P. Human atherosclerotic plaque cells and leiomyoma cells. Comparison of in vitro growth characteristics. Am J Pathol. 1975 Feb;78(2):175–190. [PMC free article] [PubMed] [Google Scholar]
  16. Moss N. S., Benditt E. P. The ultrastructure of spontaneous and experimentally induced arterial lesions. II. The spontaneous plaque in the chicken. Lab Invest. 1970 Sep;23(3):231–245. [PubMed] [Google Scholar]
  17. Peacock P. B. Atherosclerotic heart disease and the environment. Trans N Y Acad Sci. 1973 Dec;35(8):631–635. doi: 10.1111/j.2164-0947.1973.tb01536.x. [DOI] [PubMed] [Google Scholar]
  18. Selkirk J. K., Croy R. G., Roller P. P., Gelboin H. V. High-pressure liquid chromatographic analysis of benzo(alpha)pyrene metabolism and covalent binding and the mechanism of action of 7,8-benzoflavone and 1,2-epoxy-3,3,3-trichloropropane. Cancer Res. 1974 Dec;34(12):3474–3480. [PubMed] [Google Scholar]
  19. Sims P., Grover P. L. Epoxides in polycyclic aromatic hydrocarbon metabolism and carcinogenesis. Adv Cancer Res. 1974;20:165–274. doi: 10.1016/s0065-230x(08)60111-6. [DOI] [PubMed] [Google Scholar]
  20. Sims P. The metabolism of benzo[a]pyrene by rat-liver homogenates. Biochem Pharmacol. 1967 Apr;16(4):613–618. doi: 10.1016/0006-2952(67)90071-8. [DOI] [PubMed] [Google Scholar]
  21. WATTENBERG L. W., LEONG J. L., STRAND P. J. Benzpyrene hydroxylase activity in the gastrointestinal tract. Cancer Res. 1962 Oct;22:1120–1125. [PubMed] [Google Scholar]

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