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Effect of Gestational Development on Lung Tumor Size and Morphology in the Mouse

Medical College of Ohio, Department of Pathology [D. G. B., G. D. S., P. B. C., P. J. G.] and Department of Physiology [C. B.], C.S. 10008, Toledo, Ohio

Pregnant C3HeB/FeJ mice were treated with ethylnitrosourea (ENU) on one of gestation Days 10, 13, or 15 to determine if ENU treatment at different stages of gestation would result in qualitative or quantitative differences in lung tumors induced in the offspring. Lung tumors were counted and measured 6 mo after treatment with ENU. Offspring of mice treated with ENU on Day 10 of gestation had a small increase in lung tumors while those treated on gestation Day 13 or 15 had significantly more tumors than controls and 6- to 8-fold more tumors than the treated mothers. An inverse relationship between age at the time of treatment and lung tumor size was found. The mean lung tumor volume of mice exposed on Day 10 of gestation was 167-fold larger than that of mice exposed to ENU as adults. The difference between mean lung tumor volume in mice which had been exposed to ENU on Day 10, 13, or 15 of gestation appeared to be associated with the exponential growth of the fetus during this period of gestation. Lung tumors induced on Days 10 and 13 of gestation were irregular in contour and were multinodular. Sixty-five to 85% of the lung tumors in offspring treated during gestation versus 20% in mice treated as adults had a papillary morphology. These differences in tumor size and morphology indicate that cells transformed during early development may pose a greater biological hazard than cells transformed in older animals.

¹ To whom requests for reprint should be sent, at Department of Pathology and Toxicology, The Upjohn Co., Kalamazoo, MI 49001. During part of the investigation, Dr. Branstetter was a National Service Foundation postdoctoral scholar supported by Grant 5F32AM0611.

Received 4/28/87. Revised 9/22/87. Accepted 10/15/87.

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