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Biomedical subjects

P M Ingleton

Publications and source records attributed to P M Ingleton.

At least 55 records · Page 3Linked to original sources

Prolactin cells of female rats treated with the carcinogen 7,12-dimethylbenz(A) anthracene (DMBA) in vivo. An ultrastructural study.

Pituitary prolactin (PRL) cell microadenomata developed in females of a strain of Sprague-Dawley rats (SD1) following intragastric treatment with the carcinogenic hydrocarbon 7,12-dimethylbenz(a) anthracene (DMBA). Similar treatment of another strain of Sprague-Dawley rats (SD2) resulted in mammary tumour development but no PRL cell microadenomata. In SD1 strain rats morphologically distinct populations of PRL cells appeared after DMBA treatment, one composed of cells characterised by abundant, organised but very dilated RER and with large hormone storage granules, 500-600 nm in diameter (P1). The other cell type had electron-dense cytoplasm, narrow organised arrays of RER and moderately large, pleomorphic granules (P2). Both cell types appeared active with large Golgi and prominent nucleoli. P2 cells were most numerous 2 months after DMBA treatment but had virtually disappeared at 6 months and microadenomata were common at 8 months. PRL cells of SD2 rats were uniform in morphology, characterised by only moderate accumulations of RER, pleomorphic hormone storage granules, large Golgi and prominent nucleoli, and showed no close resemblance to either P1 or P2 cells of SD1 strain rats. It is possible that the morphological variations which developed in SD1 PRL cells may represent changes in responsiveness to factors controlling PRL cell secretion and proliferation and which may be pertinent to microadenoma development.

9,10-Dimethyl-1,2-benzanthracene↗

Ultrastructure of pituitary somatotrophs of male rats during liver carcinogenesis by 3'-methyl-4-dimethylaminoazobenzene.

Somatotrophs of male Wistar rats fed a carcinogenic dose of the potent hepatocarcinogen 3'methyl-4-dimethylaminoazobenzene-(3'MeDAB) in a complete diet for up to 21 weeks, showed ultrastructural changes within one week of the start of the experiment. Morphometric analysis showed that the area of the somatotrophs occupied by hormone storage granules was reduced significantly at all stages up to 21 weeks, when the experiment was terminated. The cell area occupied by rough endoplasmic reticulum (RER) was significantly increased after three weeks and RER surface density increased after eight weeks, whilst granule size was reduced after four weeks. Pituitary content of radioimmunoassayable growth hormone (RIA-GH) was also lower in treated rats than in controls, from one week after the start of the experiment, but only significantly so at eight and twelve weeks, owing to large standard errors. Serum levels of RIA-GH were similarly lower in 3'MeDAB treated rats than in controls. Withdrawal of 3'MeDAB diet after twelve weeks treatment permitted partial recovery of some cell organelles, in that the content of hormone storage granules increased and the area of the RER decreased compared to rats fed 3'MeDAB continuously. There was also a partial, but non-significant, increase in pituitary RIA-GH. The pituitaries of rats pair-fed 3'MeDAB diet for 15 weeks contained significantly less RIA-GH than matched controls. These results suggest that 3'MeDAB, or its metabolites, may react with pituitary somatotrophs and impair their ability to synthesise and secrete hormone.

Animals↗

Metabolic properties of hormonally responsive osteogenic sarcoma cells.

There is sufficient impetus from the clinical nature of osteogenic sarcoma to stimulate basic studies of the effects of hormones on tumor growth and differentiation. This can probably best be done first by the use of in vitro studies to determine precisely the effects of certain hormones on tumor cell growth and biochemical function. Such investigations would hopefully indicate the direction of in vivo work. The differentiated transplantable tumor described in this paper is clearly hormone-responsive, and offers a means of investigating the effects of other hormones, including growth hormone, androgens, estrogens and glucocorticoids, on specialized function of the osteogenic sarcoma cells, and on the growth of the tumor.

Adenylyl Cyclases↗

Radiation induced osteogenic sarcoma in the rat as a model of hormone-responsive differentiated cancer.

An osteogenic sarcoma was induced in an inbred strain of the Sprague Dawley rat using seven serial injections of 32P-orthophosphate. The tumor was maintained by transplantation over a 3-year period in the same inbred strain. During this time it retained its bone-like differentiation. Tumor membranes and freshly isolated tumor cells also retained responsiveness to parathyroid hormone and to prostaglandins of adenylate cyclase and cyclic nucleotide formation respectively. The potencies of these agents and their analogues and metabolites were found to be proportional to their efficacies as bone resorbing agents. Thus, the tumor was shown to be a model for the study of hormone-responsiveness for tumor growth and differentiation, and also of the effects of agonists which act on bone-like cells.

Adenylyl Cyclases↗

Pituitary growth hormone and somatotrophs in rats bearing chemically induced hepatomas.

Measurement of pituitary growth hormone (GH) content by polyacrylamide gel electrophoresis (PAGE) showed that rats bearing diethylnitrosamine (DENA) induced hepatomas contained significantly less GH than age-related controls. Light microscopy of these pituitaries revealed many apparently dying somatotrophs in tumour bearing rats. By electron microscopy the somatotrophs of DENA hepatoma rats were relatively inactive and some clearly dying, which could account for the reduced hormone content. However, electron microscopy of somatotrophs of rats with 2-acetyl-aminofluorene (2-AAF) hepatic tumour nodules revealed many very active cells with greatly increased content of free ribosomes and many granules poised for imminent release. Other somatotrophs of these rats showed lysosomal activity indicating reduced secretion after an active phase.

2-Acetylaminofluorene↗