Cell proliferation in dimethylhydrazine-induced colonic adenocarcinomata following cytotoxic drug treatment.

P J Tutton; D H Barkla

doi:10.1007/bf02889065

Home/Archive/PubMed

PubMed · 98910

Cell proliferation in dimethylhydrazine-induced colonic adenocarcinomata following cytotoxic drug treatment.

P J Tutton·D H Barkla

View original source ↗Export metadata ↓

Abstract

A stathmokinetic technique was used to study cell proliferation in dimethylhydrazine-induced adenocarcinomata of rat colon following treatment with cytotoxic drugs. The rate of cell division was significantly increased three days after treatment with 5,7-dihydroxytryptamine and seven days after treatment with 5-fluorouracil. Acceleration of tumour cell proliferation following 5,7-dihydroxytryptamine treatment was inhibited by treating animals with the antiseritoninergic drug Xylamidine Tosylate. Acceleration of tumour cell proliferation following 5-fluorouracil treatment was inhibited by treating animals either with the antiseritoninergic drug BW501 or with the histamine H2-receptor blocking drug Cimetidine.

Explore related subjects

5,7-Dihydroxytryptamine Adenocarcinoma Animals Antineoplastic Agents Cell Division Cimetidine Colonic Neoplasms Dimethylhydrazines Fluorouracil Male Rats Time Factors Journal Article

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

P J Tutton, D H Barkla. 1978-08-25. Cell proliferation in dimethylhydrazine-induced colonic adenocarcinomata following cytotoxic drug treatment.. https://doi.org/10.1007/bf02889065

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1992

Effect of serotonergic agents on regional concentrations of somatostatin- and neuropeptide Y-like immunoreactivities in rat brain.

A possible role for neuropeptides in affective disorders is suggested by many investigators. Somatostatin-like immunoreactivity (SS-LI) and neuropeptide Y-like immunoreactivity (NPY-LI) concentrations are demonstrated to be reduced in cerebrospinal fluid from depressed patients. We have shown that long-term treatment with serotonin uptake inhibitors, clomipramine and zimelidine, reduce brain SS-LI concentrations in the rat. We have studied the effect of serotonergic agents on regional brain SS-LI and NPY-LI concentrations in rats. Long-term treatment with 5-hydroxytryptamine (5-HTP), a serotonin precursor, caused reductions in SS- and NPY-LI levels in the hypothalamus. SS- and NPY-LI concentrations in the brain were markedly elevated by treatment with p-chlorophenylalanine, a serotonin synthesis inhibitor. Intracerebroventricular administration of 5,7-dihydroxytryptamine, a serotonin neurotoxin, resulted in elevations of both peptides in the brain. These results suggest a inhibitory role for the serotonergic system in the brain in the regulation of SS and NPY.

5,7-Dihydroxytryptamine↗

PubMed1992

Plasticity and ontogeny of the central 5-HT transporter: effect of neonatal 5,7-dihydroxytryptamine lesions in the rat.

5,7-Dihydroxytryptamine (5,7-DHT) is unique as a serotonin (5-HT) neurotoxin in that i.p. injection of neonatal rats increases concentrations of 5-HT in brainstem while depleting 5-HT in cortex, hippocampus and spinal cord. To study the mechanism of this effect we measured the 5-HT transporter or uptake site, a presynaptic marker, using [3H]paroxetine binding. There were significant regional differences in Bmax of vehicle-injected rats: brainstem, diencephalon > striatum, cortex, spinal cord > hippocampus, cerebellum. There were also regional differences in the ontogeny of bindings sites: at postnatal day 7, [3H]paroxetine sites were 39% of adult levels in cortex compared to 63% in brainstem. Thirty days after 100 mg/kg 5,7-DHT i.p., Bmax of [3H]paroxetine binding was significantly increased in brainstem (+67%) and diencephalon (+136%), whereas it decreased in cortex (-59%), hippocampus (-94%) and spinal cord (-99%), striatum (-41%) and cerebellum (-37%). KD remained unaltered. In dose-response studies (0-200 mg/kg), 50 mg/kg was the threshold dose for Bmax effects and 200 mg/kg was lethal. In weekly time-course studies, changes were apparent 1 week after 5,7-DHT lesions. Binding site increases in diencephalon and brainstem were not maximal until 3 weeks after injection, whereas percent decreases in cortical sites remained unchanged at each week studied. Lesion effects on the ontogeny of [3H]paroxetine binding sites were region-dependent: cortical sites continued to increase with age but spinal sites did not. There was no significant recovery in spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1992

Cerebrovascular nerve fibers immunoreactive for tryptophan-5-hydroxylase in the rat: distribution, putative origin and comparison with sympathetic noradrenergic nerves.

The distribution of serotonergic nerves in major basal and isolated small pial arteries (diameter > or = 50 microns) was investigated immunohistochemically using an antibody directed against tryptophan-5-hydroxylase (TPOH), the rate-limiting enzyme in the synthesis of 5-hydroxytryptamine (5-HT or serotonin), and compared to that of the noradrenergic system labeled for the selective noradrenaline (NA) synthesizing enzyme, dopamine-beta-hydroxylase (DBH). In addition, the possible peripheral and/or central origins of the cerebrovascular serotonergic (TPOH-positive) nerve fibers were examined. Strongly labeled TPOH-immunoreactive (TPOH-I) fiber bundles were observed in major basal arteries and gave rise to small varicose fibers organized in a meshwork pattern. The highest density of TPOH-I fibers was found in the middle cerebral artery followed by the anterior cerebral and the anterior communicating arteries, with a moderate to low density in the internal carotid and the vertebro-basilar trunk. Of the isolated pial arteries, only the larger ones (diameter > 75 microns) were significantly endowed with TPOH-I varicose fibers. However, free floating TPOH-I nerves were observed coursing through the pia-arachnoid membranes and reaching small pial vessels. In contrast, DBH-I nerve fibers were fine and were visualized primarily as numerous varicosities distributed in a circumferential manner around the vessel wall. A very high density of DBH-I varicosities was seen in the rostral part of the circle of Willis, with the internal carotid being the most richly supplied followed by the anterior cerebral and the anterior communicating arteries; comparatively, the middle cerebral artery was moderately innervated. The differences in distribution pattern and density between TPOH-I and DBH-I cerebrovascular fibers clearly suggest that these two innervation systems are not exactly superimposable. Superior cervical ganglionectomy caused an almost complete disappearance of TPOH-I nerves in all vascular segments, with some residual fibers in selected vessels. Lesion of the central serotonergic component with the neurotoxin 5,7-dihydroxytryptamine had virtually no effect on the TPOH-I fibers in the major basal and isolated pial arteries. These results strongly suggest that the serotonergic innervation of major cerebral as well as pial arteries has a prominent peripheral origin closely related to the sympathetic system. Processing of superior cervical ganglion slices for TPOH immunocytochemistry, however, failed to unequivocally detect TPOH-I neurons.

5,7-Dihydroxytryptamine↗