Aflatoxin B1 activation in human lung

Toxicology and Applied Pharmacology
J KellyRoger A Coulombe

Abstract

Inhalation exposure to the carcinogen aflatoxin B1 (AFB1) in certain occupations is considerable. Because circumstantial epidemiological evidence suggests that AFB1 inhalation may cause primary lung cancer, we investigated AFB1 activation by human lung microsomes. Microsomes were incubated with [3H]AFB1 (124 microM), and activation to the AFB1-8,9-epoxide was measured as the AFB1-glutathione (AFB1-GSH) conjugate by HPLC. The formation of AFB1-GSH was in the range of 0.05-0.073 fmol/mg protein/min. The role of cytochrome P450 (CYP) 3A in this activation was investigated by oxidation of nifedipine (a prototype substrate for CYP 3A), by immunoinhibition, and by immunoblot analysis. Nifedipine oxidation varied from 0.2 to 19.2 pmol/mg protein/min in microsomes from different subjects, but did not correlate with AFB1 activation. Anti-human polyclonal CYP 3A4 IgG inhibited AFB1 activation. CYP 3A isoforms were immunoestimated to be in the range of 0.01-1.90 pmol/mg protein. Neither CYP 1A2 nor associated activity was detected in the lung microsomes. These data indicate that human lung microsomes activate AFB1 to form the exo-AFB1-8,9-epoxide and that CYP(s) of the 3A subfamily may be responsible for this activity. The relatively low ...Continue Reading

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Citations

Jun 25, 2002·Journal of Toxicology and Environmental Health. Part a·Terry R Van VleetRoger A Coulombe
Nov 16, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Philip M E ProbertMatthew C Wright
Oct 26, 2012·Journal of Toxicology and Environmental Health. Part a·Susana ViegasElisabete Carolino
May 14, 2010·Research in Veterinary Science·Sumit RawalRoger Coulombe
Jun 13, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Odile CabaretStéphane Bretagne
Oct 18, 2014·The Annals of Occupational Hygiene·Susana ViegasCarla Viegas
Sep 15, 2016·Scientific Reports·Robert J LeeNoam A Cohen
Jan 8, 2008·Toxicology and Applied Pharmacology·John A GuariscoRoger A Coulombe
Aug 12, 2005·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·José V CastellMaría José Gómez-Lechón
Jun 10, 2003·Journal of Applied Toxicology : JAT·Brian M Paddle
Sep 14, 2011·Rapid Communications in Mass Spectrometry : RCM·Odile CabaretMarcel Delaforge
Nov 22, 2018·Lab on a Chip·David BovardJulia Hoeng
Oct 23, 2002·Critical Reviews in Toxicology·Janne HukkanenHannu Raunio
Dec 31, 2005·International Journal of Cancer. Journal International Du Cancer·Xiao-Yang HeJun-Yan Hong
Jul 17, 2014·Archives of Toxicology·Vlastimil DohnalKamil Kuča
Sep 13, 2019·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Ruth Nabwire WangiaJia-Sheng Wang
Feb 12, 2017·Oncology Reports·Mowaffaq Adam Ahmed AdamDoblin Anak Sandai
Nov 9, 2004·The American Journal of Clinical Nutrition·Jonathan H WilliamsDeepak Aggarwal
Jan 16, 2020·International Journal of Environmental Research and Public Health·Noreddine Benkerroum
Nov 11, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Terry R Van VleetRoger A Coulombe
May 18, 2000·Toxicology and Applied Pharmacology·P J KleinR A Coulombe
May 16, 2002·Toxicology and Applied Pharmacology·Biing-Hui LiuYi-Ling Yang
Jan 5, 2002·Journal of Pharmacological and Toxicological Methods·H PingW Meng-Chao
Jul 11, 2002·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Patrick J KleinRoger A Coulombe
Mar 28, 2003·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·P J KleinR A Coulombe
Oct 12, 2010·Chemical Research in Toxicology·Odile CabaretStéphane Bretagne

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