The lung tumor promoter, butylated hydroxytoluene (BHT), causes chronic inflammation in promotion-sensitive BALB/cByJ mice but not in promotion-resistant CXB4 mice

An inflammatory response accompanies the reversible pneumotoxicity caused b y butylated hydroxytoluene (BHT) administration to mice. Lung tumor formati on is promoted by BHT administration following an initiating agent in BALB/ cByJ mice, but not in CXB4 mice. To assess the contribution of inflammation to this differential susceptibility, we quantitatively characterized infla mmation after one 150 mg/kg body weight, followed by three weekly 200 mg/kg ip injections of BHT into male mice of both strains. This examination incl uded inflammatory cell infiltrate and protein contents in bronchoalveolar l avage (BAL) fluid, cyclooxygenase (COX)-1 and COX-2 expression in lung extr acts, and PGE(2) and PGI(2) production by isolated bronchiolar Clara cells. BAL macrophage and lymphocyte numbers increased in BALB mice (P < 0.0007 a nd 0.02, respectively), as did BAL protein content (P < 0.05), COX-1 and CO X-2 expression (P < 0.05 for each), and PGI(2) production (P < 0.05); conve rsely, these indices were not perturbed by BHT in CXB4 mice. BALB mice fed aspirin (400 mg/kg of chow) for two weeks prior to BHT treatment had reduce d inflammatory cell infiltration. Our results support a hypothesis that res istance to BHT-induced inflammation in CXB4 mice accounts, at least in part , for the lack of effect of BHT on lung tumor multiplicity in this strain. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.