Carcinomas of the respiratory tract in hamsters given arsenic trioxide and/or benzo[a]pyrene by the pulmonary route.

The pulmonary carcinogenicity of arsenic trioxide (As) alone and in combination with benzo[a]pyrene (BP) was studied in male Syrian golden hamsters given 15 weekly intratracheal instillations. The animals were divided into four groups: As, BP, As + BP, and controls. At each instillation about 3 mg/kg body wt as arsenic and/or 6 mg/kg body wt of BP was administered. All groups received a carrier dust (charcoal carbon), which increased the lung retention of arsenic, as well as sulfuric acid. Carcinomas of the larynx, trachea, bronchi, or lungs were found in 3, 17, and 25 of 47, 40, and 54 animals examined in the As, BP, and As + BP groups. No respiratory tract carcinomas were found in 53 control animals. The incidence of pulmonary adenomas, papillomas, and adenomatoid lesions was markedly higher in the As group than in the control group (P less than 0.01). Taken together the data provide strong evidence that arsenic trioxide can induce lung carcinomas. Furthermore, there was some evidence of a positive interaction between arsenic and BP in relation to adenomatous lung tumors, which could be of importance for the synergism between arsenic and smoking observed in smelter workers.