DMBA誘発副腎卒申の発症および3-MCによる予防機序に関する実験的研究

Abstract

To investigate the mechanisms of development and prevention of adrenal apoplexy induced by 7,12-dimethylbenz (a) anthracene (DMBA) in adult rats, two experiments were carried out. In the first experiment,31 JCL Sprague-Dawley female rats divided to the following 6 groups; (1) untreated control, (2) singly DMBA-intubated, (3) twice Heparin-combined, (4) twice Phenobarbital (PB) -pretreted, (5) quadruply PB-pretreated, (6) 3-Methylcholanthrene (MC) pretreated. All animals of groups (2) - (6) were intubated by DMBA,25mg, disolved in 2 ml of sesame oil on the age of 55 days. Heparin,240 units, was injected subcutaneously 15 and 24hr after the intubation of DMBA. PB,100mg/kg, was injected subcutaneously either 2 times (24 and 48 hr before the intubation) or 4 times (24,48,72 and 92 hr before the intubation). MC,80mg/ kg, was given orally with a stomach tube 48 hr before the DMBA administration. All rats were killed by decapitation 40 hr after the DMBA administration (on the age of 57days). Both adrenals were observed morphologically, and the induction rates of adrenal apoplex y in the experimental groups were obtained as follows; Control 0/8, DMBA solo 8/8, Heparincombined 10/10, twice PB-pretreated 10/10, quadruply PB-pretreated 9/10, MC-pretreated 0/16. Moreover, the histologic finding of adrenal apoplexy was more severe in the heparincombined group than the DMBA solo group. In the second experiment using adult female rats, both hepatic clearance and adrenal incorporation of tritiated DMBA were observed biochemically 1and 3 hr after the single intraperitoneal injection of 3H-DMBA,800μCi/ kg, emulsified in DMSOsaline. The radioactivities in the fresh hepatic tissues and in the organic solubent-extractable fractions from the adrenal glands were counted by a Packard liquid scintillation spectrometer, and they were calculated to dpm/mg of wet weight. In comparison of DMBA solo and PB-pretreated groups, the pretreatment of MC accerelated significantly the hepatic clearance of DMBA and decreased prominently the adrenal incorporation of DMBA and organic solubent extractable fraction of its metabolites 3 hr after the intraperitoneal administration. In conclusion, DMBAinduced adrenal apoplexy may initiate from multiple adrenocorticolytic phenomena evolked by a direct action of DMBA in inner zone of the adrenal cortex, and may develope, without an intravascular coagulation, under a special microcirculaion of the adrenal cortex. The ultimate adrenocorticolytic agent was known 7-hydroxymethyl-12-methylbenz (a) anthracene, which introduced by the hepatic metabolism of DMBA. But, the pretreatment of MC accerelates prominently the detoxication of DMBA in the liver, decreases the incorporation of DMBA in the adrenal gland, and finally prevents DMBA-induced adrenal apoplexy. PB had no effect on the accerelation of DMBA detoxication and the prevention of adrenal apoplexy by DMBA.