vitamin-k-semiquinone-radical and anthracene

Large doses of 7,12-dimethylbenz[a]anthracene (7,12-DMBA) caused the death of rats within 1 day. A small amount of any of 5 polynuclear aromatic hydrocarbons or of an aromatic amine given before the highly toxic dose of 7,12-DMBA resulted in survival for more than 2 months and the specific atrophy of testis which follows 7,12-DMBA was largely prevented. Among the protective aromatics is 7,12-DMBA itself; a small dose of 7,12-DMBA given in advance induced protection of life against an otherwise lethal dose of 7,12-DMBA but only in a proportion of the animals, and testis was not protected from injury. The highly efficient inducers of protection were condensed aromatics composed of 4 or 5 rings. Protection of life against toxicity of big doses of 7,12-DMBA by pretreatment with small doses of aromatics required time (ca. 5 to 8 hours) for its induction. Ethionine given a few minutes after a highly efficient inducer of protection, 3-methylcholanthrene (3-MC), abolished induction of protection; ethionine given 8 hours after 3-MC exerted no influence on its protective effect. A lethal dose of 7,12-DMBA resulted in a considerable reduction in incorporation of tritium in DNA from tritiated thymidine while at the same time synthesis of menadione reductase was induced in liver. A small dose of 3-MC given prior to 7,12-DMBA was advantageous in partially protecting DNA synthesis.

Topics: Aging; Animals; Anthracenes; Benz(a)Anthracenes; DNA; Humans; Hydrocarbons; Liver; Male; Metabolism; Methylcholanthrene; Oxidoreductases; Rats; Research; Testis; Thymidine; Toxicology; Tritium; Vitamin K

7,12-Dimethylbenz[a]anthracene (7,12-DMBA) exerts adrenocorticolytic effects which set it apart from all other polynuclear aromatic hydrocarbons and aromatic amines which have been investigated. Adrenal damage by this compound appears to be due to its steric and electronic properties together with its unusually high solubility in lipides. Many compounds given prior to 7,12-DMBA induced protection of adrenal. The most efficient inducers of protection are flat condensed aromatics possessing 4 or 5 rings; very small doses of these compounds were required to induce protection. Other compounds devoid of these properties induced protection but large or repeated doses were necessary. All inducers of protection had to be given prior to 7,12-DMBA to prevent adrenal necrosis; when given simultaneously with, or later than, this compound adrenal apoplexy resulted. Protective aromatics and 7,12-DMBA as well induced synthesis of menadione reductase in liver. 3-Methylcholanthrene (3-MC) induced this enzyme in many normal organs including liver, lung, adrenal, and in mammary cancer as well. dl-Ethionine under appropriate conditions of time and dosage eliminated the adrenal protection induced by aromatics and also delayed the induction of menadione reductase while depressing the amount of this enzyme which was synthesized. 7,12-DMBA caused a greatly reduced incorporation of tritium from thymidine-H(3) into washed acid-insoluble residue of adrenal. 3-MC given in advance mitigated the drastic effect of 7,12-DMBA on DNA synthesis and increased considerably the amount of tritium which was incorporated. The specific damage to adrenal by 7,12-DMBA is a direct effect on cells. Protection of adrenal is a secondary effect which requires induction of protein synthesis and it results in improvement in synthesis of DNA.

Topics: Adrenal Cortex; Adrenal Gland Diseases; Aging; Anthracenes; Barbiturates; Benz(a)Anthracenes; DNA; Ethionine; Hydrocarbons; Liver; Metabolism; NAD(P)H Dehydrogenase (Quinone); Oxidoreductases; Pharmacology; Rats; Research; Thymidine; Toxicology; Tritium; Vitamin K