A single dose, which need not be hazardous to life, of 7,12-dimethylbenz [a]anthracene (7,12-DMBA) 1 invariably, selectively and totally destroys two zones of adrenal cortex of the adult rat and induces adrenal apoplexy (1); other adrenal zones survive and fatal adrenal insufficiency does not develop. The adrenal can be protected from necrosis of this sort by any of a considerable number of aromatics in small dosage provided it is given at least a few hours before 7,12-DMBA (2). In the work now to be described a pattern of highly efficient aromatic protectors was recognized. Evidence is presented that damage inflicted by 7,12-DMBA results from direct collision with cells highly susceptible to injury by the compound, whereas protection of the adrenal induced by aromatics is a secondary effect in which synthesis of protein has critical significance.7,12-DMBA is unique insofar as it is the only compound known which totally destroys the susceptible zones of adrenal after a single dose; perdeuteration of 7,12-DMBA weakens the adrenocorticolytic effect of the parent compound. 2,2-bis(2-chlorophenyl,4-chlorophenyl)-l, 1-dichloroethane (o,pt-DDD) also kills adrenal cells in the "susceptible" zones but, despite this common effect of the two compounds, the damage inflicted by o,pr-DDD differs from that induced by 7,12-DMBA both quantitatively and qualitatively (1). Far larger doses of o,p'-DDD than of 7,12-DMBA are required to produce adrenal necrosis which is focal and patchy when it occurs after giving the chloro compound.

Progesterone stimulated the growth of mammary carcinomas previously induced by 7,12-dimethylbenz[a]anthracene (DMBA) in neonatally androgenized female Sprague-Dawley rats. This stimulatory effect appeared to depend on the action of estrogens. At 2 days of age, 199 female rats were neonatally androgenized by single sc injections of 1.25 mg testosterone propionate. At 50 days of age, all rats were given 20-mg doses of DMBA by gastric intubation. About one-half of the androgenized rats were ovariectomized at 78 days of age. Rats in test groups were given daily im injections of 10 micrograms 17 beta-estradiol or 4 mg progesterone for 228 days starting at 78 days after birth. The experiments were terminated when the rats were 300 days of age. In all androgenized rats, corpora lutea were absent. In the endrogenized rats, progesterone injection induced a significant and marked increase in the incidence of mammary carcinomas from that in the androgenized controls (3.4%) in the presence of ovaries (90%) but not in the absence of ovaries (8.7%). Estrogen injecton showed some but no significant increases in the incidence of mammary carcinoma in both ovariectomized and nonovariectomized androgenized rats (17.4 and 40.0%, respectively).

Under simple conditions which are easily satisfied, a single dose of 7,12-dimethylbenz(a)anthracenel induces mammary cancer in rat selectively, invariably, and rapidly.23 In this paper the stoichiometry of dose of 7,12-DMBA, and of frequency of its administration as well, are related to yield of mammary cancers under conditions wherein each dose of hydrocarbon evoked cancer in every rat and all doses were well tolerated by the recipient.

Gastric choriocarcinoma is a rare tumor and attracts interest because of its controversial pathogenesis. The present study reports a choriocarcinomatous change with immunocytochemically hCG-positive cells in the gastric carcinoma. The patients were males, one was 41 years old and the other 42 years old. The tumor of both cases consists of adenocarcinoma and choriocarcinoma. A sequential process of morphological transition of the adenocarcinoma to the choriocarcinoma can be traced. Indirect immunoperoxidase stain (PAP method) for human chorionic gonadotropin (hCG) demonstrates the localization of hCG in the syncytiotrophoblasts. Small number of cytotrophoblasts are weakly positive. None of the components of adenocarcinoma of both cases is positive for hCG. Human placental lactogen is not demonstrated in both cases. Stain for pregnancy specific beta-1 glycoprotein is weakly positive in the adenocarcinoma of one case but not in the choriocarcinoma. In one case, the concentration of hCG was 19.9 mIU/ml in the preoperative serum and decreased to 1.2 mIU/ml after gastrectomy. HCG production by gastric carcinoma was discussed with regard to possible pathogenesis of gastric choriocarcinoma.