POSTNATAL-DEVELOPMENT OF CYTOCHROME P4501A1 AND 2B1 IN RAT LUNG AND LIVER - EFFECT OF AGED AND DILUTED SIDESTREAM CIGARETTE-SMOKE

Earlier studies have shown that both mainstream and sidestream cigaret te smoke increase the activities of cytochrome P4501A1 and 2E1 in the lungs of adult animals; however, little information is available on th e influence of ambient levels of sidestream cigarette smoke on cytochr ome P450 monooxygenase activity in the developing lung. The present st udies were conducted to define the developmental profiles of cytochrom e P450 monooxygenases 1A1 and 2B1 in rat lung and liver and to assess the effects of aged and diluted sidestream cigarette smoke (ADSS) on t he developmental profile of these two enzymes. Accordingly, pulmonary and hepatic microsomal P4501A1 and 2B1 activities were determined by m easuring ethoxy- and pentoxyresorufin-O-delakylase (EROD and PROD, res pectively) activity in animals exposed to filtered air or ADSS from bi rth to 7, 14, 21, 50, and 100 days of age. Pulmonary P4501A1 activity in control rats was not detected until 14 days of age. Activities incr eased threefold between 14 and 21 days of age and remained unchanged t o 100 days of age. In animals exposed to ADSS from birth, pulmonary ER OD activities were detected as early as 7 days postnatal and were elev ated three- to fourfold above control at all other ages examined. Hepa tic EROD activities were unaltered by ADSS exposure, Short-term (4-day ) ADSS exposure was as effective in upregulating pulmonary microsomal EROD activities as 100-day exposures. Induction of pulmonary EROD acti vities and the associated increases in mRNA levels were dependent upon the particulate fraction. Stimulation of EROD activities in major and minor daughter subcompartments was three- to fourfold higher in ADSS- exposed animals compared to controls, while there was no induction in the trachea and less than a twofold increase in the parenchyma. Pulmon ary PROD activities developed more slowly than EROD and did not reach adult levels until Day 50, ADSS did not alter pulmonary or hepatic PRO D activities. These studies show that P4501A1 and 2B1 develop at diffe rent rates in rat lung and liver and that exposure to ADSS markedly in creases P4501A1 activities in the lung at all ages examined. (C) 1995 Academic Press, Inc.