CO-CARCINOGENIC EFFECTS OF VARIOUS AGENTS IN RATS FOLLOWING EXPOSURE TO RADON AND RADON DAUGHTERS

Combined exposure to radon and to various occupational or environmenta l airborne pollutants may lead to synergistic effects for lung cancer induction. Experimentally, a co-carcinogenic effect results in increas ed tumour incidence after combined administration of the potential car cinogens. This paper is a review based on a standardized protocol deve loped to identify potential co-carcinogenic agents, using an in vivo m odel in rats. Rats were exposed to 3.6 J h m(-3) (1000 WLM) of radon, followed by exposure to the agent to be studied. Different types of co mpounds were studied, including chemicals, mineral particles and fibre s, and diesel exhaust particulates. The greatest synergistic effects w ere observed after administration of chemical compounds known to be cy tochrome P-450 1A1 inducers which are metabolized to mutagenic or non- mutagenic forms. The results observed after treatment by cytochrome P- 450 1A1 inducers indicated that radon exposure seems to specifically i ncrease early proliferation of target cells during the co-carcinogenic process. Combined exposure to radon and tobacco smoke resulted in a m ultiplicative synergistic effect. For the same cumulative radon exposu re, the incidence of lung carcinomas increased with the cumulative exp osure to tobacco smoke. Intrapleural injection of various mineral fibr es following exposure to radon resulted only in an additive co-carcino genic effect, whereas intratracheal instillation of different minerals associated with metallic mine ores did not result in significant syne rgistic effects. Under the experimental conditions used, no synergisti c effect was observed after combined exposure to radon and diesel exha ust. Copyright (C) 1996 Elsevier Science Ltd.