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Biomedical subjects

C S Potten

Publications and source records attributed to C S Potten.

At least 289 records · Page 16Linked to original sources

Early and late incorporation of tritiated thymidine into skin cells and the presence of a long-lived G 0 -specific precursor pool.

40 min after a single injection of 50 microCi of tritiated thymidine a 3 mm punch of DBA-1 mouse skin contains about 1000 dpm. This value remains constant for at least 48 hr after injection. 50 hair follicles contain about 40 dpm, and from these values the activity calculated to reside in the basal layer of a 3 mm punch of skin is 760 dpm. These values also remain constant with time after injection. Fresh punches of skin contain much more activity. The fixative-soluble fraction (the difference between fresh and fixed values) decays slowly with time. The values for DBA-2 mice are similar. Plucking the hair from the follicles appears immediately to increase the size of the fixative-soluble fraction and decrease the fixed tissue values to about 500 dpm per punch for whole skin and about 1 dpm per 50 follicles for DBA-1. Thus almost all the activity is restricted to the epidermis. The fixative-soluble fraction returns approximately to the unplucked value between 24 and 48 hr after plucking. However, during this period the fixed tissue values are rising rapidly as stimulated cells enter S. It appears that in both strains labeled material remains available for incorporation into stimulated cells for at least 48 hr after a single injection. The amount persisting appears to decrease with time. The whole-fixed skin, the hair follicles, and the epidermis all contain cells that are capable of becoming labeled after stimulation 8-48 hr after an injection. The label in question does not become incorporated into normal cycling skin or hair follicle cells. It is concluded that the DNA precursor pool is possibly connected with G(0) cells and that both the hair follicle and the basal layer of the epidermis contain these resting cells.

Animals↗

Labeling of murine mastocytoma cells in vitro with plasma tritiated thymidine-labeled animals.

40 min after injecting tritiated thymidine into an animal, 20-30% of the total plasma radioactivity is nonvolatile. This fraction decreases to about 6% 10 hr after the injection and 3% 24 hr after the injection. There appears to be material in this nonvolatile fraction that can label mastocytoma cells in culture. The labeling indices decrease with time after injection in the same way as the nonvolatile fraction. The 40 min plasma sample contains sufficient material to allow accurate assessment of the fraction of cells in S in culture after a 6 wk exposure. The circulating material is not apparently available for incorporation into those cells in cycle in the donor animal. The material appears to be related to the G(0) cell-specific pool that has been described elsewhere. The trichloroacetic acid-soluble or ethanol-soluble nonvolatile activity appears to contain thymine, and some thymidine-phosphorylated compounds.

Animals↗

The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice.

The antioxidant pyrrolidinedithiocarbamate improves the therapeutic efficacy of 5-fluorouracil (5-FU) against HCT-15 colorectal cancer cell line xenografts in nude mice without increasing toxicity to normal intestinal or hematopoietic tissues. In the current study we have shown that a similar clinically licensed antioxidant, N-acetylcysteine (200 mg/kg), can modulate the activity of 5-FU (120 mg/kg) against HCT-15 tumor xenografts in nude mice. We demonstrate that this effect is accompanied by a sustained elevation in p53-independent apoptosis without accompanying alterations in cell cycle kinetics. Extensive tumor necrosis is also a prominent feature of treatment; however, no significant impairment of neovascularization as assessed by intratumor microvessel density occurred. We believe that the clinical efficacy of N-acetylcysteine as an adjunct to 5-FU in advanced colorectal cancer should be investigated further.

Acetylcysteine↗

Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications.

Acromegaly is an endocrine disorder characterised by sustained hypersecretion of growth hormone (GH) with concomitant elevation of insulin-like growth factor (IGF)-I, and is associated with malignancy and premature mortality from cardiovascular and respiratory diseases. In particular, there may be an increased risk of colorectal neoplasia, but the exact extent of this is contentious. Colonoscopy-based studies of adenoma prevalence rates in acromegalic patients are misleading, but population-based studies on colorectal cancer risk are more consistent - a meta-analysis estimated a pooled risk ratio of 2.04 (95 % CI: 1.32, 3.14). Possible mechanisms underlying this increased risk include direct actions as a consequence of elevated levels of circulating GH and IGF-I and/or other perturbations within the IGF system. Other possible mechanisms include altered bile acid secretion, altered cellular immunity, hyperinsulinaemia, shared genetic susceptibility and increased bowel length. However, most explanations only offer indirect evidence, and the expectation of acromegaly as a natural model of colorectal carcinogenesis has not materialised. From a clinical perspective, it seems reasonable to consider a once-only colonoscopic screening at approximately age 55 years, but potential risks and benefits should be balanced.

Acromegaly↗