LUNG-CARCINOMA AND MALIGNANT MESOTHELIOMA IN PATIENTS EXPOSED TO THOROTRAST - INCIDENCE, HISTOLOGY AND P53 STATUS

In a previous registry-based survey of 999 patients injected with alph a-emitting (ThO2)-Th-232 (Thorotrast), we identified elevated risks fo r lung carcinoma and malignant mesothelioma. Since injected Thorotrast is retained lifelong mostly in liver, spleen and lymph nodes, the mes othelial surfaces of these organs are constantly irradiated. Thorotras t-administered patients also perpetually exhale Rn-220, a Th-232-daugh ter. Study of Thorotrast-exposed patients may, therefore, provide data with regard to carcinogenicity of radon exposure, a current public he alth concern, as well as the pathogenesis of malignant mesothelioma Th e incidence and histologic types of rung carcinoma and malignant mesot helioma within the cohort were examined by review of available histopa thologic material and medical records. Further, mutations of the p53 g ene were analyzed whenever possible as it has previously been suggeste d that radon-associated lung carcinomas exhibit specific mutational pa tterns. The cumulative risk for lung carcinoma reached 11.0% based on 20 confirmed cases. Nine were small cell rung cancer (SCLC), whereas t he expected frequency was 18%. The risk for malignant mesothelioma rea ched 2.5% based on 7 cases. The actuarial risk of malignant mesothelio ma for patients given more than 20 ml Thorotrast was 7.8% compared to 1.4% for patients administered smaller amounts. Seven lung carcinomas and 5 malignant mesotheliomas were analyzed for p53 mutations; only I (in a lung adenocarcinoma) was detected. A possible association betwee n Thorotrast and SCLC is suggested. In addition, a possible dose-respo nse gradient exists for Thorotrast and malignant mesothelioma. (C) 199 5 Wiley-Liss, Inc.