The effect of inhaled sulfur dioxide and systemic sulfite on the induction of lung carcinoma in rats by benzo[a]pyrene

In a previous study at this Institute, inhaled sulfur dioxide (SO2) was shown to enhance the induction by inhaled benzo[a]pyrene (BaP) of squamous cell carcinoma (SQCA) of the respiratory tract of rats (S. Laskin, M. Kuschner, A. Sellakumar, and G. V. Katz, 1976, In “Air Pollution and the Lung,” pp. 190–213). We attempted to confirm and extend this finding by using an experimental protocol intended to illuminate the role of SO2. Rats were treated with BaP by 15 consecutive weekly intratracheal instillations. Some of these rats were simultaneously exposed either to SO2 by inhalation or to sulfite/bisulfite anions that accumulated systemically from endogenous generation in rats with induced sulfite oxidase deficiency. The total treatment period spanned 21 weeks, after which the rats were observed for the development of tumors. BaP-treated rats began to die with SQCA of the respiratory tract at approximately 200 days after the first BaP treatment and at 2 years after the first treatment nearly all rats in the BaP-treated groups had died, most with SQCA. Survival in the control groups was excellent and the health of all groups (aside from pulmonary SQCA in BaP-treated groups) was also excellent. The probability of dying with a pulmonary SQCA in the experimental groups treated with BaP, BaP plus inhaled SO2, and BaP plus systemic sulfite/bisulfite was calculated by the logrank analysis. The data sets of SQCA probability from these groups were not statistically different (i.e., P > 0.05) by the x2 test indicating that, in this experiment, neither inhalation exposure to SO2 nor systemic exposure to sulfite/bisulfite anions affected the induction of SQCA of the lung by intratracheally instilled BaP. We conclude that the results of this study do not support an etiological role for either SO2 or sulfite/bisulfite anions in the induction of SQCA of the respiratory tract by BaP.