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Quantitative Analysis of Genetic Susceptibility to Liver and Lung Carcinogenesis in Mice¹

Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan 20133, Italy

One-week-old male and female mice of the A, BALB/c (C), and C3H/He (C3) strains and of the AC3 and CC3 F₁ hybrids were treated with a single dose (300 mg/kg s.c.) of urethan and then kept without further treatment until 30 and 40 weeks (males) or 30 and 65 weeks (females). The degree of difference in susceptibility to hepatocarcinogenesis between the susceptible C3 and the resistant A and C mice, in the different age and sex groups, was 4–12-fold by the analysis of the number of nodules/cm³ (N/cm³), which represents an estimation of tumor frequency and was more than 400-fold as indicated by the percentage of liver volume occupied by nodules (V%), an estimation of tumor size. With regard to lung carcinogenesis, mice of the A strain proved 5–10- and 20–70-fold more susceptible than the C and the C3 mice, respectively, as indicated by the number of microscopically identified lung tumors/mouse (N), an estimation of tumor frequency. The lung tumor size, as estimated by the mean tumor volume (V), was similar in A and C mice but much higher in the A than in the C3 groups (13-1000-fold difference). The AC3 hybrid was highly susceptible to both liver and lung carcinogenesis. The CC3 hybrid was as susceptible to lung carcinogenesis as its C parent and had an intermediate susceptibility to hepatocarcinogenesis. Our results indicate that a major determinant in the genetic susceptibility to hepatocarcinogenesis, and perhaps to lung carcinogenesis too, is tumor growth, as evidenced by a much greater tumor size in genetically susceptible than resistant mice.

¹ This work was supported in part by grants from PF CNR "Oncologia" and Associazione Italiana Ricerca Cancro.

² To whom requests for reprints should be addressed, at Istituto Nazionale Tumori, Via G. Venezian 1, 20133, Milan, Italy.

Received 5/ 1/91. Accepted 9/19/91.

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