Butylated hydroxytoluene (BHT) induction of pulmonary inflammation: A rolein tumor promotion

Chronic pulmonary inflammatory diseases predispose towards lung cancer by u nknown mechanisms. Butylated hydroxytoluene (BHT) administration to mice ca uses lung injury and a subsequent inflammatory response, and when administe red chronically to certain inbred strains following carcinogen treatment, i ncreases lung tumor multiplicity. We hypothesize that inflammation promotes lung tumor growth in this model system and have begun to examine this hypo thesis by assessing inflammatory;parameters in inbred strains that vary in their susceptibility to promotion. Positive correlations were found between susceptibilities to tumor promotion and BHT induction of alveolar macropha ge and lymphocyte infiltration into alveolar airspaces, and increased vascu lar permeability (P < .03, P < .04, and P < .005, respectively). The amount s of pulmonary cyclooxygenase (COX)-1 and COX-2 did not strongly correlate with promotion. Because persistent elevation of macrophage content is the h allmark of a chronic inflammatory response, the alveolar macrophage populat ion was depleted by adding chlorine to the drinking water prior to carcinog enesis. This treatment reduced lung tumor multiplicity following 2-stage ca rcinogenesis. These correlations between inflammatory and tumorigenic respo nses to BHT, along with decreased tumorigenesis after macrophage depletion, are consistent with a rob of inflammation in promotion. Inflammatory media tors may provide targets for early diagnosis and chemoprevention.