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Biomedical subjects

M B Shimkin

Publications and source records attributed to M B Shimkin.

At least 55 records · Page 3Linked to original sources

Selective inhibition of growth by the proline analogue thiazolidine-4-carboxylic acid and its probable mode of action in Saccharomyces cerevisiae.

Cells of Saccharomyces cerevisiae showed differential growth inhibition when cultured on various carbon sources in the presence of the proline analogue thiazolidine-4-carboxylic acid (TZ). On 0.5% yeast extract, 2% glucose and TZ (10 mg/ml) medium, growth lags from 8 to 10 h were observed, after which cells recovered and growth proceeded normally. Growth was totally inhibited on a medium of 0.5% yeast extract, 3% ethanol, and 5 mg of TZ per ml. This inhibition was not due to the inability of cells to undergo aerobic respiration, since similar media containing glycerol instead of ethanol allowed growth. Proline added to the culture medium reversed the lag on glucose and TZ medium but did not promote recovery on ethanol and TZ medium. TZ was found to have two probable modes of action in yeast. It was a noncompetitive inhibitor of yeast alcohol dehydrogenase, and it was also found to be incorporated into cellular protein. Uptake studies using (14)C-labeled TZ showed that the recovery on glucose was correlated with the progressive exclusion of the analogue from cells.

Carboxylic Acids↗

Funding: grants or contracts? A survey of cancer scientists.

The members of the American Association for Cancer Research (AACR) were polled for their reactions to the current controversy of funding by research grant versus that by the research contract and to the nature of the scientific review appropriate for the evaluation of both types of applications. About 50% of the members responded; 97% of these felt that additional basic knowledge was absolutely essential or probably essential for the successful pursuit of the goals of the National Cancer Program. Eighty % of the respondents concluded that the funding of such research programs should be derived largely from grants rather than contracts. Most of the participants agreed that there should be a major rather than a minor redistribution of funds toward grants and away from contracts. About 50% of the respondent AACR members currently are being supported by research grants, about 10% receive contracts only, and another 25% of the members have both types of funds at their disposal. The group of contract-supported scientists felt less critical of contracts, but about one-half of that group also wished to see more funds going into the grant rather than into the contract programs for the additional support of basic research. There was considerable agreement among all groups of respondents that the review process for contracts should make much more active use of extramural peer evaluation to eliminate scientific inequities now existing between the two instruments for funding of work in cancer research.

Humans↗

Bioassay of alkyl halides and nucleotide base analogs by pulmonary tumor response in strain A mice.

The production of lung adenomas in strain A mice following multiple injections of 17 alkyl halides and of 3 base analogs was investigated. A slight but significant increase in the average number of lung tumors per mouse was noted following the administration of methyl iodide, n- and i-propyl iodide, sec- and tert-butyl chloride, i-, sec-, and tert-butyl bromide, and n- and sec-butyl iodide. The administration of comparable doses of ethyl bromide, ethyl iodide, n-butyl chloride, benzyl chloride, and 1-chloromethylnaphthalene to mice resulted in no significant increase in the frequency of lung tumors over that seen in vehicle-treated control mice. n-Butyl bromide and tert-butyl iodide similarly appeared to have no significant effect on the lung tumor frequency, but these compounds were too toxic to be tested at the high dosages used with the other alkyl halides. 5-Iodo-, 5-bromo-, and 5-fluorodeoxyuridine also appeared to have no significant effect on the lung tumor frequency. These results indicate that a high proportion of low-molecular-weight alkyl halides may be weakly carcinogenic and provide evidence supporting an electrophilic hypothesis of carcinogenesis.

Adenoma↗