Studies on cigarettes smoke carcinogenesis using trensgenic mouse with human c-Ha-ras gene contained somatically activated transgenes.

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Relationship between passive smoking and human lung cancer by epidemiologicalsurvy have been reported. On the other hand, the relation was not clear by inhalation experiment of cigarette smoke to animal. Transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 60% of transgenicoffspring had tumor with 18 months. The aim of this investigation is effected or not effected on somatic mutation and tumor of cigarette smoke using transgenic mice with human c-Ha-ras gene contained. First and second experiment ; Transgenic mice and non-transgenic mice were exposed main stream of cigarette 'smoke which was 10 or 5 times dilluted with fresh air. This study were conducted that 20 cigarettes smoke were exposed in 3 days per week. The difference of mice weight between cigarette smoke exposed group and non-exposed group were not shown. Malignant tumor was not observed both transgenic and non-transgenic mouse in cigarette exposure groups. Third experiment ; Transgenic mice were exposed with 80 cigarettes smoke in 3 days per week. Adenocarcinoma was observed in the lung of one of exposed transgenic mouse. And two non-exposed transgenic mice were also observed adenocarcinoma in the lungs. These malignant tumor were analyzed using PCR followed by oligonucleotide hybridization. As a result, c-Ha-ras genes wre observed in these three lungs.