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Biomedical subjects

M R Alison

Publications and source records attributed to M R Alison.

84 records · Page 5Linked to original sources
PubMed1979

Differential lethal effects of both cytosine arabinoside and hydroxyurea on jejunal crypt cells and testosterone-stimulated accessory sex glands.

DNA-synthesizing cells from mouse jejunal crypts and accessory sex glands respond differently to the DNA synthesis inhibitors cytosine arabinoside and hydroxyurea. A single injection of either agent brought about a rapid inhibition of thymidine labelling in both the tissues. Whilst both agents had a lethal effect upon the majority of S-phase cells in the crypts, only a minority of S-phase cells in the accessory sex glands showed evidence of necrosis. These differences are considered in the context of possible physiological differences between continually dividing cells and putative G0 cells. The accessory sex glands are normally quiescent proliferative tissues. They were stimulated to undergo DNA synthesis and later mitosis by testosterone propionate injections, commencing three days after castration. Cytosine arabinoside was the more effective cytocidal agent in the accessory sex glands, and when two injections were scheduled so as to affect a large number of DNA-synthesizing cells, a compensatory hyperplasia was evoked. In the coagulating gland, this compensatory response involved the proliferation of many cells which, in the absence of cytotoxic perturbation, would be non-proliferatie (Q cells).

Animals↗
PubMed1979

Testosterone 5 alpha-reductase activity as related to proliferative status in mouse accessory sex glands.

Testosterone 5 alpha-reductase activity has been measured during the proliferative response of the seminal vesicle and coagulating gland of the castrated mouse after continuous treatment with tesotsterone. Daily subcutaneous injections were begun either 3 or 14 days after castration. At 3 days after castration, a pre-replicative period of 50-60 h occurred before the onset of DNA synthesis, and a continuous [3H]thymidine labelling procedure revealed that only a minority of epithelial cells were subsequently involved in the transitory proliferative response. At 14 days after castration, cells were able to prepare more quickly for DNA synthesis (20-30 h), and the subsequent proliferative response involved a higher proportion of the epithelial cells present. At 14 days after castration, testosterone treatment resulted in the activity of the enzyme/mg homogenate increasing fourfold in the seminal vesicle and tenfold in the coagulating gland, to values almost double those of control (intact animals. At 3 days after castration, testosterone treatment resulted in much slower increases in enzyme activity, and at the completion of day 5 of treatment, levels were close to control values. It is concluded that a relationship may exist between the initial increase in 5 alpha-reductase activity and the duration of the pre-replicative period before DNA synthesis begins. Although testosterone and its resultant effects upon 5 alpha-reductase activity are clearly implicated in the genesis of the proliferative response, the ultimate control of cell proliferation must be independent of androgenic hormones. When cell division was effectively curtailed at the completion of day 4 of testosterone treatment, abnormally high levels of enzyme activity were still present.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1976

Cell proliferation in the prostate complex of the castrate mouse.

Cell proliferation during 100 h of continuous androgen challenge was studied in the seminal vesicle and coagulating gland of Balb/c mice castrated 3 days or 14 days prior to the first daily injection of 250 mug testosterone propionate. Continuous labelling with [3H] thymidine indicated that the seminal vesicle was almost totally responsive to androgen, as early as 3 days after castration, whereas the androgen sensitivity of the coagulating gland increased from 30% at 3 days after castration to 85% at 14 days after castration. In both tissues the magnitude of the proliferative reaction could be related to the extent of cell loss prior to stimulation. The duration of the pre-replicative phase in the response of the seminal vesicle to androgen was 20-25 h both at 3 and 14 days after castration. In the coagulating gland the pre-replicative phase was 40 h at 3 days after castration and 20 h at 14 days after castration. The maximum uptake of [7alpha-3H] testosterone administered to mice 3 days after castration was significantly greater (P less than 0-01) in the seminal vesicle compared to the coagulating gland. At 14 days the seminal vesicle and coagulating gland exhibited a similar capacity for uptake. The in vivo metabolism of [7alpha-3H] testosterone was studied by thin layer chromatography 30 min and 120 min after administration. A high proportion of the radioactivity extracted from all the tissues was associated with highly polar steroids. At 3 days after castration, the seminal vesicle, 2 h after administration of radioactive testosterone, retained a much higher proportion of radioactivity associated with dihydrotestosterone than did the coagulating gland. The localization of steroid in mice 3 days after castration was studied by dry-mount autoradiography at intervals up to 2 h after the injection of [1,2,6,7(n)-3H]-testosterone. A heavier deposition of silver grains was observed over autoradiographs of the seminal vesicle. In the seminal vesicle the grains were primarily located over nuclear areas whereas in the coagulating gland the grains were diffusely distributed over both nuclear areas and over cytoplasmic areas.

Animals↗
PubMed1975

The proliferative response of the coagulating gland of the castrated mouse under continuous androgen stimulation: an experimental and computer simulation model.

The proliferative response of the coagulating gland of the castrated male mouse has been examined during continuous treatment with testosterone propionate. Fourteen days after castration, s.c. daily injections of testosterone propionate were begun. Mitotic (Im) and labelling (IL) index values were obtained at 3 h intervals for up to 100 h after the initial injection. These showed a biphasic response, in which IL reached a maximum at 30 and 70 h, and Im at approximately 45 and 75 h. Fraction-labelled mitoses (FLM) curves were begun 24, 48, and 72 h after the first androgen injection. In each curve the first wave of labelled mitoses rose to 100% and showed a square form indicating little spread in the durations of the G2 and S phases. Values of 7.5, 1.3 and 0.7 h were obtained for the durations of DNA synthesis (ts), the post-synthetic period (tG2) and of mitosis (tm) respectively. In none of the FLM curves was it possible to demonstrate a second wave of labelled mitoses and direct measurement of the cell cycle time (Tc) was not obtained. Continuous tritiated thymidine labelling indices revealed that after a latent period of 25 h, DNA synthesis began and labelling rose rapidly to 80% by 45 h and then more slowly to 95% by 97 h. Cell population changes during androgen stimulation estimated from measurements of total glandular DNA indicated that the number of cells present in the glands remained constant during the first 30 h after stimulation and thereafter increased to approximately 2-3 times the original value. The data are compared with a mathematical model which assumes that the cell population of castrated mice when stimulated passes from a GO compartment through successive waves of DNA synthesis and mitosis. After each cell division the cells may leave or remain in the proliferative cycle. This model has been subjected to computer simulation using the cell cycle parameters obtained in the kinetic experiments. There was good agreement between the stimulation and experimental results in the Im and IL curves, continuous labelling, and total cell number experiments. The simulation of FLM curves was less successful. Although the first wave of labelled mitoses was clearly seen the model predicts a distinct second wave of labelled mitoses. It is concluded that this does not appear because of variation in the duration of G1.

Animals↗
PubMedDate not supplied

Growth factors and growth factor receptors.

Peptide growth factors and their cell surface-associated receptors are important determinants of normal and pathological growth reactions. Through signal transduction pathways, receptor occupancy triggers the production of intracellular downstream effector molecules which ultimately cause cell proliferation.

Cell Communication↗