SELECTIVE ADRENAL NECROSIS AND APOPLEXY INDUCED BY 7,12-DIMETHYLBENZ(a)ANTHRACENE

Abstract

In the work now to be described, it was observed that a single dose of 7,12-dimethylbenz(a)anthracenO caused extraordinary changes in the rat consisting of adrenal apoplexy and massive necrosis in the two inner zones of the cortex while other regions of the adrenal glands were uninjured. In addition to the selectivity of the anatomic site of damage, there is high specificity of the molecular structure of the polynuclear aromatic hydrocarbon exerting this adrenocortieolyfic effect.Earlier it was found (1, 2) that a single dose of any of a number of polynuclear aromatic hydrocarbons, under special circumstances, selectively induced mammary cancer in every rat with very great rapidity. DMBA was the most effective of these compounds and tumors arose following a solitary feeding or an intravenous injection. At necropsy of rats with cancer of the breast induced by a solitary dose of DMBA which had been administered a few weeks previously, it was observed that the adrenal glands of most of the animals were calcified. The adrenals of rats bearing mammary cancer induced by hydrocarbons other than DMBA were not calcified. It was soon found that adrenal apoplexy and necrosis were produced invariably with DMBA soon after giving the hydrocarbon. This is a newly recognized property of DMBA.Several methods were employed in these experiments for detection and measurement of damage to the adrenal glands. These included: (a) direct inspection of the gland; (b) histological observation; (c) estimation of the amount of blood pigments; (d) determination of enzyme content of the adrenals; (e) roentgenologic detection of adrenal calcification.

Effects of Hypothyroidism and Progesterone on Mammary Tumours Induced by 7,12-Dimethylbenz(a)anthracene in Sprague-Dawley Rats

“…However, neither thyroxine nor 1311 administration to DMBA-fed rats results in tumour development in the absence of the ovaries (Grice et al, 1966) and the work of Sterental et al (1963) suggests that this may be due to lack of secretion of one or more anterior pituitary hormones. Histological examination of endocrine glands from hypothyroid rats in the present series supports this last suggestion since, although changes were observed in both the pituitary and adrenal glands, the adrenal alterations appeared irrelevant to mammary carcinogenesis as such changes were present in all 4 groups and are well recognized in rats following DMBA administration (Huggins and Morii, 1961;Cefis and Goodall, 1965). Further, adrenalectomy has not been found to affect DMBA mammary tumorigenesis significantly (Jabara and Harcourt, 1971).…”

Biochemical Sequences in the Transformation of Normal Fibroblasts in Adolescent Rats

“…There was a considerable increase in incorpora- tion of day [8][9][10]. The values for 32p remained on a high plateau from days 10 to 21.…”

“…The optimal time for harvest of newly created cartilage, devoid of bone, was day [7][8]. To obtain bone without cartilage, days 18-21 were advantageous for harvest.…”

“…Homogenates were centrifuged at 12,000 X g for 15 min at 20; the supernatant was removed for enzyme assays. One unit of alkaline phosphatase (EC 3.1.3.1) was defined as the enzyme activity that liberated 1 sAmol of p-nitrophenol per 0.5 hr under stated conditions (8).…”

Hundred Day Leukemia: Preferential Induction in Rat by Pulse-Doses of 7,8,12-Trimethylbenz(a)anthracene

“…1 These compounds are of exceptional interest: (a) they are the most potent polycyclic hydrocarbons in inducing tumors, and (b) they selectively destroy the middle layer of the adrenals of adult rats (2,3). Schurr (4) devised a method to prepare rather concentrated lipid emulsions of hydrocarbons (0.5-1.0% w/w) suitable for intravenous injections.…”