@article {ROBERTSON662, author = {IAIN G. C. ROBERTSON and RICHARD M. PHILPOT and ERROL ZEIGER and C. ROLAND WOLF}, title = {Specificity of Rabbit Pulmonary Cytochrome P-450 Isozymes in the Activation of Several Aromatic Amines and Aflatoxin B1}, volume = {20}, number = {3}, pages = {662--668}, year = {1981}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The involvement of pulmonary or hepatic cytochrome P-450 monooxygenase enzymes in the activation of the promutagens 2-aminoanthracene, 2-aminofluorene, 2-acetylaminofluorene, and aflatoxin B1 has been investigated using Salmonella strain TA98. These agents were more readily metabolized to mutagenic products by the 16,000 x g supernatant fraction from lung than from liver despite the low pulmonary cytochrome P-450 content, and more revertants per nanomole of total cytochrome P-450 were consistently obtained with pulmonary than with hepatic microsomal preparations. In reconstituted monooxygenase systems containing the major pulmonary cytochrome P-450 isozymes (P-450I or P-450II), P-450II was highly effective in the activation of 2-aminoanthracene and 2-aminofluorene and also active with 2-acetylaminofluorene, whereas these substrates were not activated by P-450I. This difference was confirmed by the results of antibody inhibition studies carried out with pulmonary microsomal preparations. The higher activity of pulmonary preparations relative to hepatic preparations can be accounted for by the relatively high proportion of P-450II in the lung (approximately 50\% total cytochrome P-450 content) as compared with the liver (less than 5\%). However, antibody to P-450II did inhibit the hepatic microsomal activities by 50-70\%, indicating that P-450II may be important in the activation of these agents in both tissues even though it is a minor component in the liver. Aflatoxin B1 was activated only by P-450I in reconstituted monooxygenase systems, although the antibody inhibition studies indicated activation by both P-450I and P-450II in pulmonary microsomal preparations. ACKNOWLEDGMENTS We gratefully thank Mr. Zadock McCoy and Ms. Barbara Bynum for their expert assistance.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/20/3/662}, eprint = {https://molpharm.aspetjournals.org/content/20/3/662.full.pdf}, journal = {Molecular Pharmacology} }