AROMATIC-INDUCED PREVENTION OF FATAL TOXICITY OF 7,12-DIMETHYLBENZ[a]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.