ACCESSORY MAMMALIAN REPRODUCTIVE GLANDS 



431 



to the })rol)lcm of hormonal control of pros- 

 tatic cancer in man. 



The first induction of prostatic cancer in 

 rodents was accomplished by Moore and 

 Melchionna (1937) who injected benzpy- 

 rene in lard directly into the rat anterior 

 prostate (it should be noted that Moore and 

 ]\Ielchionna used "anterior" in the sense of 

 ventral as indicated by their histologic de- 

 scriptions of a characteristic clear zone in 

 the peripheral cytoplasm of the epithelial 

 cells; this is typical only of the ventral 

 lobe). The treatment was followed within 

 210 days by the development of squamous 

 cell carcinomas in 72 per cent, and sarcomas 

 in 5 per cent, of intact rats. Essentially simi- 

 lar results were obtained in an equivalent 

 number of rats castrated at the time of car- 

 cinogen injection. Castration after tumors 

 had developed did not cause atrophy of tu- 

 mor cells. No metastases were found but 

 there was anaplasia of cells and the tumors 

 were invasive. The squamous metaplasia 

 occurred in columnar secretory epithelium 

 which was close to, or in contact with, benz- 

 pyrene cysts. The sequence of changes was 

 reduction in cell height, loss of the clear 

 area in the peripheral cytoplasm, pseudo- 

 stratification, true stratification, develop- 

 ment of intercellular bridges, and formation 

 of keratohyaline. It was concluded that 

 testicular androgen is not an important fac- 

 tor in the development of these squamous 

 cell carcinomas, but on the basis of a small 

 series of experimental animals it was sug- 

 gested that exogenous androgen treatment 

 in castrates may increase the incidence of 

 sarcomas. 



In 1946, Dunning, Curtis and Segaloff im- 

 planted compressed methylcholanthrene 

 l)ellets into rat prostates (lobe not specified) 

 and induced metastasizing squamous cell 

 carcinomas. The tumors were transplant- 

 able and metastasized equally well in male 

 and female hosts. Bern and Levy (1952) in- 

 jected methylcholanthrene in lard into ven- 

 tral prostates of intact Long-Evans rats 

 and induced extensive neoplasms within 7 

 to 9 months. All but one were squamous cell 

 carcinomas; the exception was a sarcoma. 

 Quantitative determinations of enzyme ac- 

 tivity showed a loss of alkaline phosphatase 

 in cancerous prostates but no significant 

 changes in acid phosphatase activity. Histo- 



chemically, the stroma and capillaries were 

 alkaline phosphatase reactive, but the car- 

 cinomas had virtually lost the strong alka- 

 line phosphatase activity of the epithelium 

 of origin (Table 6.2). There was some pseu- 

 doreaction or reaction in sloughed keratin 

 and necrotic areas. 



Allen (1953) injected a suspension of 

 methylcholanthrene in distilled water into 

 ventral prostates or coagulating glands of 

 intact and castrated rats. All were autop- 

 sied 180 days later. A high percentage of 

 squamous cell carcinomas and a few sar- 

 comas developed; metastases occurred in a 

 few cases. There was no statistically signifi- 

 cant difference between tumor incidence in 

 the ventral prostate and coagulating gland. 

 Tumors of the ventral prostate were found 

 in 70.6 per cent of the intact rats and in 100 

 per cent of the castrates; in castrates in- 

 jected with testosterone propionate there 

 were tumors in 57.7 per cent of the animals, 

 and in castrates treated with estradiol ben- 

 zoate, 77.8 per cent. It was concluded that 

 tumor incidence was highest in castrates 

 and lowest in intact males or castrates 

 treated with testosterone propionate, and 

 that estrogen did not affect tumor incidence. 

 ]\Iirand and Staubitz (1956) placed methyl- 

 cholanthrene crystals in ventral prostates of 

 99 intact Wistar rats and observed the ef- 

 fects for over 300 days. The resulting tu- 

 mors were classified as 30 squamous cell 

 carcinomas, 3 leiomyosarcomas, and 2 ade- 

 nocarcinomas; squamous cell carcinomas 

 and adenocarcinomas metastasized. Frag- 

 ments of squamous cell carcinomas were 

 transplanted and survived and metastasized 

 more successfully in males than in females. 



Horning (1946) imjiregnated strips of 

 tissue from mouse dorsal prostates and an- 

 terior prostates (coagulating glands) with 

 crystals of methylcholanthrene and in- 

 serted them as subcutaneous homografts 

 into intact males. By this method adeno- 

 carcinomas were induced in grafts of both 

 dorsal prostate and coagulating gland. 



In mice of the RIII and Strong A strains 

 (Horning and Dmochowski, 1947) methyl- 

 cholanthrene in lard was injected into dor- 

 sal and anterior prostates (coagulating 

 glands). Squamous cell carcinomas and sar- 

 comas developed in Strong A mice, but only 

 sarcomas in RIII. Squamous metaplasia of 



