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Quantitative Evaluation of Growth Rates in Tumors before and after Radiation^*

(From the Cancer Research Laboratory, Dept. of Hospitals, City of N.Y., and the Dept. of Biology, Graduate School of Arts and Science, N.Y.U., N.Y.)

Attempts were made to evaluate the rates of growth of tumors before and after radiation on a quantitative biological basis. Chalkley's method, which permits a quantitative evaluation of spatial distribution of morphologic tissue components in an extended volume of tissue, was used for this study.

Two mammary tumors of the Bar Harbor strains of mice, dba and C3H, both diagnosed as adenocarcinomas and referred to in the text as the dbrB and C3H tumors, respectively, were employed as test objects. Analysis of five dbrB tumors yielded an average ratio of mitotic to resting cells of 1:49.6 (range: 1:43.8–1:53.8), while analysis of five mammary tumors of the C3H strain yielded an average ratio of mitotic to resting cells of 1:72.5 (range: 1:63.6–1:87.5). It is indicated that the relatively greater increase in size of the dbrB mammary tumor, as compared to the C3H tumor, is due not only to the greater mitotic activity of this tumor but also to its inherent secretory tendency, which produces engorgement of the glandular lumina. Consequently, it is thought advisable to take such a biological characteristic into consideration in evaluating the increase in tumor size as measured externally.

Volume ratios of mitotic to intact resting cells of five dbrB tumors, exposed to various doses of x-radiation and removed following various periods of time, are presented. Microscopic fields of stained sections of intact portions of the tumor, chosen at random, were used for analysis. A decrease in mitotic activity was noted which depended upon the dose of irradiation applied and the lapse of time between exposure and removal of the tumors. For example, 1 mitotic figure to 41.0 resting cells was found in the intact portions of a dbrB tumor 24 hours following a dose of 5,000 r; a ratio of 1:87.5 was found in another dbrB tumor which received the same dose of radiation but which was removed 13 days following exposure. The ratio of 1:41.0 is very close to the range of mitotic indices found in untreated dbrB tumors, while the ratio of 1:87.5 indicates a decrease in mitotic activity as compared to the normal. A delayed effect is indicated.

The effectiveness of a large dose of radiation is illustrated by the ratio of 1 mitotic figure to 350 resting cells found in a dbrB tumor which was removed and fixed 22 hours following irradiation with 16,000 r.

The results obtained indicate the possibility of applying Chalkley's method to the quantitative evaluation of growth rates of tumors, taking the mitotic index as a criterion. This method also proved helpful in evaluating the effectiveness of a given dose of radiation on a quantitative basis.

^* This study is part of a project on classification of tumors according to their rates of growth, metabolic activities, and radiosensitivities, which is supported by grants from the National Cancer Institute, Public Health Service, and from the Damon Runyon Memorial Fund.

Received 10/ 6/50.