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Interactions between tumor-promoting agents and histones studied by circular dichroism.

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As part of an attempt to uncover the molecular basis of tumor promotion, the effects of the tumor promoters 12-0-tetradecanoylphorbol-13-acetate (TPA), sodium dodecyl sulfate, cholic acid and polyoxyethylene sorbitan monostearate (Tween 60) on conformations of histones in 0.14 M NaF, pH 7.8, were studied by the circular dichroism technique. A common property of the promoters was their ability to increase the asymmetric environment of the aromatic side chains of "inner histones" H2B and H4 and a H2A - H4 mixture. TPA was effective at TPA/histone molar ratios as low as 0.03. The order of activity of TPA and Tween 60 resembled their activity in tumor promotion, i.e., TPA much greater than Tween 60. TPA and Tween 60 had no effects on the tertiary structure of "outer histone" H1.

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