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Sensitivity of a Lung Cell in the Developing Mouse Embryo to Tumor Induction by Urethan¹

First Department of Surgery, Osaka University Medical School, Dôjima-hamadôri 3-12, Fukushima-ku, Osaka 553, Japan

Urethan, administered to pregnant mice at various stages of pregnancy, induced lung tumors in their offspring with high frequency. Consequently, the sensitivity of a lung cell to tumor induction by urethan was analyzed in relation to its differentiation, utilizing urethan's unique characteristics of fast action and unrestricted placental penetration. The sensitivity was calculated by the ratio of the number of tumors per lung to the weight (mg) of the lung at the time of urethan exposure, because there was a direct correlation between the number of tumors and the weight of the lung lobe at the time of exposure. The sensitivity of a lung cell was inversely proportional to the degree of the differentiation of the fetal lung. This finding is compatible with the law of Bergonié and Tribondeau for radiation biology. When urethan was given to pregnant mice just before delivery, tumor frequency in their offspring was 10 times higher than when given on Day 19 of gestation. However, this contradiction disappeared when the effective retention period of urethan in the fetus just before birth (approximately 10 times longer than in the fetus on Day 19) was taken into account, because tumor frequency was directly proportional to the dose of urethan and the frequency of the treatment. In this investigation, the weight of the lung was used as a measure of the total number of lung cells. Therefore, an interpretation of a hit theory in a cell level may be proposed according to these findings. Histological patterns of induced lung tumors were correlated to the size of tumors.

¹ This is Paper 3 of the series entitled "Transplacental Carcinogenesis by Urethan in Mice" and was presented at the 30th Annual Meeting of the Japanese Cancer Association (1971). This work was supported by grants-in-aid for Cancer Research from the Japanese Ministry of Education, Osaka Tai-Gan Kyokai, Japan, and Shôni-no Gan-o Mamoru-kai, Japan.

² Present address: Institute for Cancer Research, Osaka University Medical School, Dôjima-hamadôri 3-12, Fukushima-ku, Osaka 553, Japan.

Received 1/26/73. Accepted 8/14/74.