Strain A mouse pulmonary tumor test results for chemicals previously tested in the National Cancer Institute carcinogenicity tests.

Sixty-five chemicals were coded and examined for their ability to induce lung tumors in strain A/St (laboratory A) or strain A/J (laboratory B) mice. Thirty-five chemicals were tested in laboratory A only, 6 in laboratory B only, and 24 in both laboratories. Two-year carcinogenicity test results as well as genotoxicity test data are available for most of these chemicals. There was poor interlaboratory agreement in strain A test results for the 24 chemicals tested in both laboratories. In addition, there was poor agreement between strain A test results from either laboratory and 2-year carcinogenicity test results or genotoxicity results. Possible explanations for these findings include selection of a large number of aromatic amines in the group of chemicals submitted for strain A testing, differences in strain A testing protocols and in statistical analysis of results from the two laboratories, low sensitivity of the strain A/St mice used in this particular study, and general problems inherent in comparing any relatively short-term animal tumor model with 2-year carcinogenicity tests. Since there is no absolute reference for carcinogenicity, no one test system is better than another. Carcinogenicity test data are relevant only to the test model employed.

Classics in oncology. Survival in untreated and treated cancer.

During 1935 to 1951, a total of 75,494 cancer cases occurred among the inhabitants of Connecticut, of whom there were 2,000,000 in 1950. The five-year survival rate has improved gradually from 12 and 19 percent of all males and females, respectively, in 1935 to 1940, to 20 and 32 percent, respectively, during 1947 to 1951. This improvement is not due to earlier diagnosis of the cases, as can be seen from the similar distribution of localized and disseminated cases during the whole period of study. The improvement has occurred in cancer that is diagnosed when it is clinically localized and when it involves regional areas, but not when it is disseminated. The most marked improvement is recorded for cancers of the colon and rectum in both sexes, and of the uterine cervix in women. The data are compared with survival rates anticipated in untreated neoplastic disease. A new era of detection and treatment of cancer is being entered through the studies on in situ and occult cancers among the population.

Inhibition by magnesium and calcium acetates of lead subacetate- and nickel acetate-induced lung tumors in strain A mice.

The ability of the physiologically essential divalent metals calcium and magnesium to inhibit the tumorigenic activities of lead and nickel towards the lungs of strain A mice was investigated. The tumorigenic salts lead(II) subacetate and nickel(II) acetate were injected i.p. at their maximal tolerated doses (0.04 mmol/kg/injection of each metal) for a total of 24 injections, whenever possible. Calcium(II) acetate and magnesium(II) acetate were administered in the same preparation along with the lead and nickel salts at molar doses of approximately 1, 3, 10, and 30 times the maximal tolerated dose of the tumorigen. The animals were sacrificed 30 weeks after the first injection, and the lung tumors were counted. The lead and nickel salts, administered alone, each produced a significant increase in the observed number of lung adenomas per mouse. When administered with any of the doses of calcium acetate or magnesium acetate tested, neither lead subacetate nor nickel acetate showed any significant tumorigenic activity. Calcium acetate alone (total dose, 11 mmol/kg of body weight) appeared to yield a significant rise in lung adenomas observed. The results indicate an antagonism between magnesium and calcium and the tumorigenic metals nickel and lead.

Pulmonary adenoma response of strain A mice to sulfonic acid derivatives of 1- and 2-naphthylamines.

Various sulfonic acid derivatives of 1-naphthylamine and 2-naphthylamine were tested in inbred A/St (male and female) mice by the pulmonary adenoma bioassay to determine if this class of compounds, used as intermediates in the dye-stuff industry, possesses tumorigenic activity. Neither 1-naphthylamine nor the four sulfonic acid derivatives of 1-naphthylamine tested were tumorigenic. However, 2-naphthylamine and two of the three sulfonic acid derivatives of 2-naphthylamine tested produced statistically significant lung tumor responses at comparable doses. These results indicated that this class of compounds should be examined more extensively for carcinogenic activity.

Increase in testis luteinizing hormone receptor by estrogen in mice susceptible to Leydig cell tumors.

In an investigation comparing two strains of mice (BALB/c, susceptible to estrogen-induced Leydig cell tumors and C3H, resistant to such tumors), we found that the Leydig cell-luteinizing hormone (LH) receptors increase in BALB/c mice and decrease in C3H mice during estrogen treatment. In the BALB/c strain, LH receptor content in the tested of mice treated 1, 2, 4, 6, or 8 weeks with diethylstilbestrol (DES) was 2.4- to 5.4-fold greater than that in the testes of untreated littermates. By 24 weeks of treatment, the receptor number had increased 10-fold. Likewise, two weeks of estradiol benzoate treatment in BALB/c mice resulted in a dose-dependent increase in LH receptor content. In contrast, in C3H mice, DES treatment resulted in a transient initial increase (60%), followed by a time-dependent decrease in testicular LH receptor number: 38 and 17% that of normal by six and eight weeks of treatment, respectively. In both strains of mice, DES-induced changes in 125I-labeled human chorionic gonadotropin binding reflected changes in LH receptor number rather than in receptor affinity (approximately 3 x 10(-11) M). The testis weights of BALB/c mice remained normal during DES treatment, whereas those of the C3H decreased with time. Sprague-Dawley rats, resistant to estrogen-induced Leydig cell tumors, like C3H mice, also underwent testicular atrophy and lost LH receptors during DES treatment. The present study demonstrates that estrogen treatment indices diametrically oppossed change in testicular LH receptor number in the two strains of mice with different susceptibilities to Leydig cell tumorigenesis.

Effect of commercial saccharin preparations on urethan-induced lung tumorigenesis in strain A mice.

The effect of commercial saccharin preparations on urethan-induced mouse lung tumorigenesis was assessed by gavaging groups of male strain A mice with 1-g/kg doses of each saccharin preparation on a daily basis 5 days/week. Gavage was initiated 1 week before i.p. injection of either a low (0.1 mg/g) or a high (1 mg/g) dose of urethan and continued until the mice were sacrificed 16 weeks after urethan administration. The average number of surface lung tumors per mouse for each group of mice was determined and was compared statistically with the appropriate control group. The commercial saccharin preparations did not produce an elevated lung tumor response when administered alone. One of the four saccharin preparations enhanced the lung tumor response to urethan when given in conjunction with the low dose of urethan, but this enhancement was not statistically significant. At the high urethan dose, all saccharin preparations produced a statistically significant enhancement of the lung tumor response to urethan.

Effect of lactate dehydrogenase virus on chemically induced mouse lung tumorigenesis.

Lactate dehydrogenase virus is the third in a series of viruses which have been examined for the capacity to alter chemically induced mouse lung tumorigenesis. This virus was given to strain A mice by i.p. injection either 4 weeks before, on the same days as, 4 weeks after, or 8 weeks after the s.c. injection of urethan (either 0.25 or 1.0 mg/g). The pulmonary adenoma response to urethan was suppressed in all of the lactate dehydrogenase-infected mice, with a maximum suppression of 30 to 40% when the virus was given simultaneously with or 4 weeks after urethan. As with murine sarcoma virus and reovirus, it is postulated that this suppression of chemically induced mouse lung tumorigenesis is due to virally induced alterations in the immune response of the mouse to chemically induced tumors.

Committee on Growth, 1945-1956: another noble experiment.

The events of the creation, activities, and termination of the Committee on Growth of the National Research Council as the advisory body on research to the American Cancer Society, 1945 to 1956, are historical and instructive. It remains to be demonstrated that programmed research support is more effective than the less structured approaches represented by the Committee on Growth.

Scanning electron microscope surface morphometry of type II alveolar lung cell response to urethane in strain A mice.

Quantitative scanning electron microscope (SEM) examination of the time course of type II cell hyperplasia in mice exposed to a single i.p. injection of urethane is presented. Counts of type II cells from random alveoli suggest that, compared to controls, a significant depression in type II cell numbers occurs during the first week, followed by a doubling in the next 3 to 4 week period. This supports conclusions of earlier studies done with thin sections and light morphometric techniques. The use of a SEM as the morphometric tool is statistically more efficient, however, since initial sample preparation is easier, samples are larger in area, resolution is higher and, most importantly, the amount of surface area available for examination is many times greater than that presented by light microscope examination of cross sections with equivalent magnification.