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Quantitative Analysis of the Time-dependent Development of Glucose-6-phosphatase-deficient Foci in the Livers of Mice Treated Neonatally with Diethylnitrosamine¹

McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706

The development of glucose-6-phosphatase (G-6-Pase-)-deficient hyperbasophilic foci was analyzed at 4-week intervals in the livers of CD-1 and C57BL/6J x C3H/HeJ F₁ (hereafter called B6C3F₁) mice given a single i.p. injection of diethylnitrosamine (DEN) (0.1, 0.2, or 0.4 µmol/g body weight) within 24 hr after birth. Transections of G-6-Pase-deficient foci of hepatocytes were readily discernible in liver sections of DEN-treated mice of either sex at 8 weeks of age. The size and number of these foci per liver increased with time. The occurrence of G-6-Pase-deficient focus transections with diameters as large as 1 mm coincided with the gross appearance of 1-mm gray-white nodules in the livers of male B6C3F₁ mice at 16 weeks of age and in females at 32 weeks of age. Transections of all grossly visible hepatic nodules from male and female mice were G-6-Pase deficient and hyperbasophilic; the great majority were diagnosed as mouse hepatomas type A.

After a single neonatal dose of DEN, the number and rate of growth of the G-6-Pase-deficient foci and the incidence and rate of appearance of gross hepatomas were greater in the livers of male than in those of female mice. In contrast, the average numbers of G-6-Pase-deficient foci in the livers of male and androgenized female B6C3F₁ mice at 36 weeks of age were approximately equal and about twice that observed for the livers of DEN-treated female controls.

Quantitation of carcinogen-induced histochemically detectable foci and hepatomas as a function of time provides a useful tool for the analysis of initiation and promotion in the mouse liver.

¹ This work was supported by Grants CA-07175, CA-22484, and CA-09135 from the National Cancer Institute, USPHS.

² Present address: Department of Chemistry and Metabolism, Litton-Bionetics, 5516 Nicholson Lane, Kensington, Md. 20795.

³ Present address: Carcinogenesis Laboratory, Fee Hall, Michigan State University, East Lansing, Mich. 48824.

⁴ To whom requests for reprints should be addressed.

Received 4/28/80. Accepted 1/21/81.

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