Lost colony: Laboratory of Experimental Oncology, San Francisco, 1947--54: historical note.
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Biomedical subjects
Publications and source records attributed to M B Shimkin.
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The i.p. injection of caffeine (8, 20, and 40 mg/kg) 3 times weekly for 8 weeks suppressed the development of spontaneous pulmonary adenomas in strain A mice. The same caffeine injection scheme suppressed urethan (0.25 and 1.0 mg/g)-induced lung tumor development when caffeine treatment started 1 week before urethan administration, but this suppression was not significant when caffeine treatment was initiated 1 week after urethan injection. The most pronounced suppression of lung tumor formation occurred when caffeine was given as only two injections 3 hr before and 3 hr after urethan administration. The incorporation of [3H]thymidine into lung tissue DNA of caffeine-treated mice was impaired at the time of urethan administration. Also, caffeine partially antagonized the effects of urethan on lung tissue, as measured by [3H]thymidine incorporation studies. One interpretation of these results is that caffeine-induced suppression of DNA synthesis interferes with pulmonary adenoma induction by decreasing the affinity of lung tissue DNA for urethan. The finding that chronic caffeine treatment produced continued suppression of [3H]thymidine incorporation into lung tissue DNA suggests that caffeine-induced inhibition of spontaneous pulmonary adenoma formation is due to a general suppression of lung DNA-synthetic activity.
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Two studies tested the ability of metals and their salts to produce lung tumors in strain A mice. Of 13 compounds examined, lead subacetate, manganous sulfate, molybdenum trioxide, and nickelous acetate elicited a weakly carcinogenic response following intraperitoneal injection. Nine metallic compounds were negative. There was no evidence of cocarcinogenic effect between metals and the chemical carcinogen, 3-methylcholanthrene. On the basis of these and other data, recommendation is made for further investigations in metal carcinogenesis.
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An in vitro-in vivo system for screening potentially effective drugs against solid tumors is described. Drug toxicity to plateau-phase pulmonary adenoma cells is used as an in vitro screen for potential activity against solid tumors, since both plateau phase cultured cell populations and solid tumors are composed predominantly of nondividing cells. The effect of drugs with in vitro activity on the rate of appearance of urethan-induced adenomas on the lung surface of strain A mice in vivo is used to assess drug efficacy in the treatment of solid tumors, taking into consideration drug toxicity to and drug metabolism by the host. Arabinosylcytosine and hydroxyurea were ineffective against plateau phase cells in vitro, even at high concentrations (5 to 10 mg/ml), and did not affect pulmonary adenoma growth in vivo, even at toxic doses (arabinosylcytosine, 80 mg/kg; hydroxyurea, 800 mg/kg), as would be expected with these cell cycle-active drugs. Adriamycin, an effective agent against human solid tumors, was cytotoxic to plateau phase cultured cells (0% survivors at 1 mug/ml), and a dose of 2 mg/kg completely inhibited pulmonary adenoma growth in mice. Thus, this pulmonary adenoma bioassay would appear to effectively select for drugs which may be active against solid tumors in humans.
The production of lung adenomas in strain A following multiple i.p. injections of selected organic water contaminants was investigated. Of the 16 contaminants tested, only bromoform produced a pulmonary adenoma response that was significantly greater than the pulmonary adenoma response of vehicle-treated control mice.
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There have been real and heartening advances in the diagnosis and treatment of breast cancer during the past 20 years. A greater proportion of women with breast cancer can now be detected before cancer has metastasized. Some patients with breast cancer can now be cured by systemic chemotherapy. Much of the problem still remains to be researched, but the control of breast cancer can be realistically predicted.
The production of lung adenomas in strain A mice following multiple i.p. injections of 13 metallic compounds was investigated. A significant increase in the average number of lung tumors per mouse was noted following the administration of lead subacetate, manganous sulfate, molybdenum trioxide, and nickelous acetate. These four compounds can be considered as weakly carcinogenic for lung tumors in strain A mice.
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