COCARCINOGENIC EFFECT OF CYTOCHROME-P-450 1A1 INDUCERS FOR EPIDERMOIDLUNG-TUMOR INDUCTION IN RATS PREVIOUSLY EXPOSED TO RADON

The aim of this work was to characterise the cocarcinogenic effect of CYP1A1 inducers in male Sprague-Dawley rats previously exposed to 1000 WLM radon. Three inducers were used: methylcholanthrene (MC), metabol ised by CYP1A1 into strong mutagenic compounds; 5,6-benzoflavone (beta NF) metabolised into non-mutagenic compounds; and 2,3,7,8 tetrachloro benzo-p-dioxin (TCDD) regarded as non-mutagenic and non-metabolised. T hese inducers were administered by six repeated intramuscular injectio ns of 25, 25 and 0.0013 mg per kg respectively at 2-week intervals. Ra ts were studied 1 or 4 months after the end of the treatments. A cocar cinogenic effect was observed for each compound corresponding to speci fic occurrences of squamous cell carcinoma. Latency periods for about 100% tumour induction were about 100 days for MC and beta NF but incre ased to 200 days for TCDD. Biochemical studies have shown a similar gl obal CYP1A1 induction for each treatment corresponding to about 40 tim es the control value. Immunohistolocalisation of CYP1A1 was confined t o some bronchial cells in controls whereas it was clearly demonstrated after each chemical treatment in hyperplastic epithelial foci.