INTERACTION OF 4-METHYLBENZALDEHYDE WITH RABBIT PULMONARY CYTOCHROME-P-450 IN THE INTACT ANIMAL, MICROSOMES, AND PURIFIED SYSTEMS - DESTRUCTIVE AND PROTECTIVE REACTIONS

The metabolism of some chemicals by the pulmonary cytochrome P-450-dependent mono-oxygenase system is thought to be a requisite step in the development of some pulmonary and respiratory tract cancers and aromatic hydrocarbon related bronchiolar necrosis. About 50% of rabbit pulmonary cytochrome P-450 is destroyed by treatment of the intact animal, microsomes, or systems reconstituted from purified pulmonary mono-oxygenase components with 4-methylbenzaldehyde. The loss of the cytochrome is accompanied by an equimolar loss of heme. The action of 4-methylbenzaldehyde requires the presence of NADPH and O2 appears to result from cytochrome P-450 catalyzed metabolism. Selective destruction of one of the known forms of rabbit pulmonary cytochrome P-450 does not account for the lack of complete destruction of pulmonary P-450 by 4-methylbenzaldehyde; loss of about 50% of each form of the cytochrome occurs in vivo and in reconstituted systems. Form II is affected to a greater extent than form I when microsomes are incubated with 4-methylbenzaldehyde. The portion of the cytochrome not degraded by 4-methylbenzaldehyde appears to be protected by some factor produced from 4-methylbenzaldehyde during the incubation. This factor also protects against complete destruction of the cytochrome by cumene hydroperoxide.