Studies on 2,6‐diaminopurine and related substances in cultures of embryonic and sarcomatous rodent tissues

Biesele, John J.; Berger, Ruth E.; Wilson, Anne Yates; Hitchings, George H.; Elion, Gertrude B.

doi:10.1002/1097-0142(195101)4:1<186::aid-cncr2820040123>3.0.co;2-#

Cited by 39 publications

(7 citation statements)

References 17 publications

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“…The effect was equivalent to that attained with 5 mM a-ketobutyrate. Relative superiority of adenine to hypoxanthine and adenosine in antagonizing 2,6-diamino-purine in sarcoma 180 and embryonic mouse skin cultures has been reported, however ( 16). This was surprising for adenine and adenosine have proved interchangeable in satisfying nutritional and metabolic requirements of cell cultures( 13, 14).…”

Section: Phenethylbiguanidementioning

confidence: 99%

Inhibitory Effects of Hadacidin on KB Cell Cultures.

Neuman

Tytell

1963

Experimental Biology and Medicine

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57 ture at onset of feeding is unexplainable at present. At first it was believed to be related to the fact that the animal consumed most of his daily water intake during the feeding session, since the water was at room temperature, some 15°C below body temperature. This explanation was checked by feeding and withholding water; under such conditions the fall was still observed though somewhat attenuated. However, a similar fall with a subsequent rise in hypothalamic temperature was also observed when the animal's arms were held and he struggled. In fact, any sudden increase in the animal's activity level was usually accompanied by the initial fall and then a rise in temperature. These transients of hypothalamic temperature may be better explained in the future by observations of blood flow to the area. As McCook et al.(3) have suggested, the temperature of the hypothalamus should be determined not only by its rate of heat produc-tion, but also by the blood flow through it. I t appears that caution is needed when making inferences about thermoregulation solely from hypothalamic temperature. Summary.Continuous recordings of hypothalamic temperature were made on a rhesus monkey placed in a restraining chair. Under non-isolated conditions distinct diurnal variations in temperature were observed. The extent of these cycles appeared to be attenuated when the animal was isolated. In addition, feeding sessipns under isolated conditions were accompanied by larger increases in temperature than during non-isolated condi tions.

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Section: Phenethylbiguanidementioning

confidence: 99%

Inhibitory Effects of Hadacidin on KB Cell Cultures.

Neuman

Tytell

1963

Experimental Biology and Medicine

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“…Burchenal et al (6) showed that large doses of DAP could increase the survival time of leukemic mice. Biesele et aL (7) discovered that DAP differentially damaged cultures of normal and sarcomatous mouse and rat tissues and damage was prevented by adenine. The authors suggest that the primary effect was probably not through desoxypentosenucleic acid.…”

Section: Introductionmentioning

confidence: 99%

Cytological Studies on the Antimetabolite Action of 2,6-Diaminopurine in Vicia Faba Roots

Setterfield

Duncan

1955

The Journal of Cell Biology

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At a concentration of 9.6 x 10–5 M, 2,6-diaminopurine (DAP) completely inhibited cell enlargement, cell division, and DNA synthesis (determined by microphotometric measurement of Feulgen dye) in Vicia faba roots. Inhibition of cell enlargement was partially reversed by adenine, guanine, xanthine, adenosine, and desoxyadenosine. Guanine and the nucleosides gave the greatest reversal, suggesting that one point of DAP action upon cell enlargement is a disruption of nucleoside or nucleotide metabolism, possibly during pentosenucleic acid synthesis. DAP inhibited cell division by preventing onset of prophase. At the concentrations used it had no significant effect on the rate or appearance of mitoses in progress. Inhibition of entrance into prophase was not directly due to inhibition of DNA synthesis since approximately half of the inhibited nuclei had the doubled (4C) amount of DNA. Adenine competitively reversed DAP inhibition of cell division, giving an inhibition index of about 0.5. Guanine gave a slight reversal while xanthine, hypoxanthine, adenosine, and desoxyadenosine were inactive. A basic need for free adenine for the onset of mitosis was suggested by this reversal pattern. Meristems treated with DAP contained almost no nuclei with intermediate amounts of DNA, indicating that DAP prevented the onset of DNA synthesis while allowing that underway to reach completion. The inhibition of DNA synthesis was reversed by adenine, adenosine, and desoxyadenosine although synthesis appeared to proceed at a slower rate in reversals than in controls. Inhibition of DNA synthesis by DAP is probably through nucleoside or nucleotide metabolism. A small general depression of DNA content of nuclei in the reversal treatments was observed. This deviation from DNA "constancy" cannot be adequately explained at present although it may be a result of direct incorporation of DAP into DNA. The possible purine precursor, 4-amino-5-imidazolecarboxamide gave no reversal of DAP inhibition of cell elongation and cell division and only a slight possible reversal of inhibition of DNA synthesis.

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“…Conceivably, such toxicity comparisons could be carried out in a number of ways, more or less of equal validity a priori. Our procedure, which has been described elsewhere (Biesele, 1951;Biesele et al, 1951), may be summarized as follows:…”

Section: Methodsmentioning

confidence: 99%