Test for carcinogenicity of metallic compounds by the pulmonary tumor response in strain A mice.

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.

Diethylpyrocarbonate, a histidine selective reagent, inhibits progestin binding to chick oviduct cytosol.

In this report we describe experiments showing that diethylpyrocarbonate, a histidine selective reagent, inhibits progestin binding to the chick oviduct progesterone receptor. Because this inhibition is reversed by hydroxylamine, we suggest that the chick oviduct progesterone receptor contains one or more histidine residues that regulate progestin binding. We also find that the progestin R5020 protects the progesterone receptor from diethylpyrocarbonate mediated inhibition of progestin binding. From this we infer that the progestin binding site contains a histidine residue(s) important for progesterone binding to its receptor in chick oviduct.

Chick oviduct progesterone receptor binding of 15 beta, 17-dihydroxyprogesterone and its analogues.

We have tested derivatives of progesterone obtained by fermentation with Aspergillus giganteus for relative binding affinity for the progesterone receptor of chick oviduct. Our studies show that hydroxyl and oxo substitutents at C-11 and C-15 of progesterone significantly decrease the hormone's affinity for the progesterone receptor. The loss in affinity on introduction of a C-15 hydroxyl in 17-hydroxyprogesterone is restored by acetylation to 15 beta-acetoxy-17 hydroxyprogesterone. The latter compound may have some potential as an in vivo agent.

Diethyl pyrocarbonate, a histidine selective reagent, inhibits estrogen binding to receptor protein in rat uterus cytosol.

We find that at pH 6.1 diethyl pyrocarbonate inhibits estrogen binding to its receptor protein in rat uterus. Hydroxylamine partially reverses this inhibition and estrogen partially protects its receptor protein from this inhibition. We suggest that the estrogen receptor protein in rat uterus contains a nucleophilic site that either overlaps or is near the estrogen binding site. Based on the pH of inhibition reaction, the receptor concentration in the experiment, and the partial reversal of the inhibition by hydroxylamine, we suggest that this site contains a histidine residue or possibly an unusually reactive tyrosine residue that is important for estrogen binding.