Study of the combined action of inhaled plutonium oxide and two chemical carcinogens present in the environment

The modifications of risk attributable to two carcinogens present in the environment - benzopyrene (BP) and dimethylnitrosamine (DMNA) - following inhalation of plutonium oxide have been studied in rats. BP (2x5 mg) was given intratracheally in association with Fe2O3, 2 and 3 weeks after inhalation of PuO2. DMNA (2 or 20 ppm) was added to the animals' drinking water. The results show, for BP, a strong synergistic effect which manifests itself in a substantial reduction of lifetime in animals that have inhaled a small quantity of PuO2 (17 nCi), and in a greater incidence of tumours and enhanced tumour invasiveness whatever the dose of PuO2 inhaled. Inhalation of PuO2 associated with regular ingestion of DMNA multiplies the metastases of liver cancers in the lung. Addition of BP or DMNA modifies the histological profile of radiation-induced tumours. The synergistic effects are no longer observed when the pollutant concentrations used produce subacute intoxication. (author)