Omeprazole and ranitidine, antisecretagogues with different modes of action, are equally effective in causing hyperplasia of enterochromaffin-like cells in rat stomach

Female rats were treated for 28 days with high doses of the gastric acid secretion inhibitors omeprazole and ranitidine. Omeprazole, which is long-acting, was given orally once daily. Ranitidine, which is short-acting, was given by continuous infusion (via osmotic minipumps, implanted subcutaneously). The aim was to produce a similar degree of acid inhibition with the two drugs. The inhibition of acid secretion over the day and night was more pronounced in the omeprazole-treated rats (maximal inhibition 100%, minimum 85%) than in those receiving ranitidine (mean 70%). In both groups, there was a great increase in plasma gastrin, somewhat greater after omeprazole than after ranitidine. The gastrin concentration in the antrum was almost doubled by both treatments and there was a moderate increase in the number of antral gastrin cells in the omeprazole-treated rats. The number of enterochromaffin-like (ECL) cells (per visual field) increased in the oxyntic mucosa to the same extent (greater than 100%) in the ranitidine- and omeprazole-treated rats. Apart from the gastrin cells in the antrum and the ECL cells in the corpus no other gastric endocrine cell type seemed to respond to treatments with antisecretagogues. We conclude that, regardless of the type of antisecretagogue used, effective and long-term suppression of gastric acid secretion results in sustained hypergastrinemia and increased number of ECL cells. Conceivably therefore, the ECL cell hyperplasia reflects the trophic effect of gastrin.     

Gastro-protective effect of methanol extract of Ficus asperifolia bark on indomethacin-induced gastric ulcer in rats

The gastro-protective and antioxidant effects of methanol extract of Ficus asperifolia bark on indomethacin induced gastric ulcer were investigated in male rats. Thirty two male rats divided into 4 equal groups and were treated as follows: group1 (control), 0.5ml of 5% tween 80 (vehicle for the extract), groups 2 and 3, 100 and 500mg/kg of Ficus asperifolia extract respectively and group 4, cimetidine (100mg/kg). After two weeks of daily oral administration of vehicle, extract or cimetidine, gastric ulcer was induced in all rats with indomethacin (40 mg/kg, p.o). Gastric juice pH, gastric acid concentration, gastric ulcer score, percentage gastric ulcer inhibition, activity levels of superoxide dismutase (SOD), catalase and malondiadehyde (MDA) were determined. Ficus asperifolia extract significantly increased gastric pH (p.     

Characterization of "unhealed gastric ulcers" produced with chronic exposure of acetic acid ulcers to indomethacin in rats.

We previously discovered that a 4-wk course of indomethacin delivered to rats with acetic acid ulcers resulted in production of "unhealed gastric ulcers" that persisted for up to 12 wks after treatment cessation. The present study examined the mechanism underlying such "unhealed gastric ulcers" with biochemical and histological procedures. "Unhealed gastric ulcers" were induced with a 4-wk indomethacin treatment (1 mg/kg, twice daily) in rats with acetic acid ulcers. Two and 4 wks after treatment cessation, ulcer size was significantly larger in rats receiving indomethacin compared with control animals. Ulcerated tissue prostaglandin E2 levels were significantly lower during indomethacin treatment, but the levels tended to increase after treatment cessation compared with levels measure in the group receiving vehicle. Myeloperoxidase activity levels were significantly higher during indomethacin treatment; such levels persisted after treatment cessation. Histologically, greater degrees of fibrosis and neutrophil accumulation, as well as a lesser degree of angiogenesis were observed in the "unhealed gastric ulcers" compared to ulcers that healed in a normal fashion. It was concluded that severe fibrosis, persistent neutrophil infiltration, and poor angiogenesis in the ulcer base might represent factors involved in the mechanism underlying production of "unhealed gastric ulcers".     

Aspirin suppresses 1,2-dimethylhydrazine-induced alteration of proliferative parameters in rat colonic crypts

Abstract. Human epidemiological reports and rodent experimental research data indicate a possible chemopreventive effect of regular aspirin use for decreasing risk of colon and rectum cancer incidence and mortality. We have previously demonstrated that aspirin can significantly suppress proliferative parameters in normal rat colonic epithelium when examined 24 h following an acute or chronic course of aspirin administration. To investigate whether aspirin would effectively suppress known carcinogen-induced changes in colonic epithelium, rats were given single s.c. injections of either aspirin (50 mg/kg bw) or saline on days 1–3 and either 1,2-dimethylhydrazine (DMH; 12 mg base/kg bw) or DMH vehicle on day 4 of each week for eight consecutive weeks. Rats were sacrificed 4 days after the last aspirin dose and 3 days after the last DMH or DMH vehicle dose. Using the proliferative biomarkers of proliferating cell nuclear antigen positive cells per midaxial crypt section (SCC), crypt proliferative zone height (PZ), crypt differentiated zone height (DZ), and total crypt height (CH), it was found that aspirin does suppress DMH-induced increases in SCC, PZ and CH. The findings demonstrate that aspirin has a long term (i.e. several days) protective effect against early carcinogen-induced proliferative changes in rat colonic crypts which may help account for aspirin's chemopreventive action against colon cancer.     

Preventive Effects of Tocotrienol on Stress-Induced Gastric Mucosal Lesions and Its Relation to Oxidative and Inflammatory Biomarkers

This study aimed to investigate the possible gastroprotective effect of tocotrienol against water-immersion restraint stress (WIRS) induced gastric ulcers in rats by measuring its effect on gastric mucosal nitric oxide (NO), oxidative stress, and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) orally. After 28 days, rats from one control group and both treated groups were subjected to WIRS for 3.5 hours once. Malondialdehyde (MDA), NO content, and superoxide dismutase (SOD) activity were assayed in gastric tissue homogenates. Gastric tissue SOD, iNOS, TNF-α and IL1-β expression were measured. WIRS increased the gastric MDA, NO, and pro-inflammatory cytokines levels significantly when compared to the non-stressed control group. Administration of tocotrienol and omeprazole displayed significant protection against gastric ulcers induced by exposure to WIRS by correction of both ulcer score and MDA content. Tissue content of TNF-α and SOD activity were markedly reduced by the treatment with tocotrienol but not omeprazole. Tocotrienol significantly corrected nitrite to near normal levels and attenuated iNOS gene expression, which was upregulated in this ulcer model. In conclusion, oral supplementation with tocotrienol provides a gastroprotective effect in WIRS-induced ulcers. Gastroprotection is mediated through 1) free radical scavenging activity, 2) the increase in gastric mucosal antioxidant enzyme activity, 3) normalisation of gastric mucosal NO through reduction of iNOS expression, and 4) attenuation of inflammatory cytokines. In comparison to omeprazole, it exerts similar effectiveness but has a more diverse mechanism of protection, particularly through its effect on NO, SOD activity, and TNF-α.     

Pathological features of the colonic tumours induced in rats by the administration of 1,2-dimethylhydrazine.

The parenteral administration of 1,2-dimethylhydrazine to rats caused the development of colonic neoplasms in about 90% of animals by 24--30 weeks of treatment. Usually there were multiple tumours with a mean of 2.7 per rat. The lesions have been classified histologically into adenomata (26% of all tumours) and carcinomata, the latter showing varying degrees of differentiation. No completely anaplastic tumours were seen, and there were none originating in connective tissue. The distributions of the different tumour types along the length of the colon varied. The more benign lesions were situated predominantly in the distal half of the colon, while the poorly differentiated adenocarcinomata were concentrated in the proximal third of the colon. There was good evidence to suggest that adenomata often progressed to frank malignancy in the distal colon. In the proximal part, however, it appeared that tumours frequently developed de novo as poorly differentiated carcinomata. Perhaps regional variations in the kinetic organisation of the normal colonic mucosa somehow influence the nature of the neoplastic change induced by DMH, thus accounting for the differences in tumor distribution. After 24 weeks of DMH treatment there was only a small increase in the mean number of tumours per rat.     

Gastrin effects on isolated rat enterochromaffin-like cells following long-term hypergastrinaemia in vivo.

The enterochromaffin-like (ECL) cells play an important role in the regulation of gastric acid secretion. They respond to gastrin by a prompt increase in histamine secretion, an effect which is mediated by the CCK-(B)/gastrin receptor acting through the IP(3)/DAG pathway. In the rat, long-term treatment with acid secretion inhibitors induces hypergastrinaemia which, in turn, results in ECL cell hypertrophy and hyperplasia. The aim of the present study was to evaluate various functional parameters in acutely isolated rat ECL cells, following long-term hypergastrinaemia in vivo. Rats were treated with vehicle or a supramaximal daily dose of omeprazole for more than 10 weeks to ensure ECL cell hyperplasia. ECL cells were isolated from vehicle-treated animals and 24, 72 and 120 h after the last dose of omeprazole. The functional activity of the acutely isolated ECL cells was determined by measuring gastrin-and forskolin-induced histamine secretion. Changes in cytosolic free calcium upon gastrin stimulation were monitored by digital video imaging. ECL cells successively regained their ability to respond to gastrin following long-term hypergastrinaemia, reaching close to vehicle-treated levels 120 h after the last dose of omeprazole. In the rat, the response pattern of the ECL cells appears to normalise in parallel with the normalisation of plasma gastrin levels.     

Therapy effect of antiulcer agents on new chronic cysteamine colon lesion in rat

After demonstration that cysteamine induced duodenal lesions in gastrectomized rats, while a number of antiulcer drugs mitigated these lesions, it was shown that one single intrarectal (i.r.) cysteamine application produced severe colon lesions in acute studies in rats. Thus, the further focus was on the protracted effect of cysteamine challenge (400 mg/kg b.w. i.r.) and therapy influence in chronic experiments in female rats. Regularly, cysteamine colon lesions were markedly mitigated by ranitidine (10), omeprazole (10), atropine (10), methylprednisolone (1), sulphasalazine (50; mg/kg), pentadecapeptide BPC 157 (PL-10, PLD-116; 10 microg or 10 ng/kg). Specifically, after 1 or 3 months following initial challenge (cysteamine 400 mg/kg i.r.) in female rat, the therapy [BPC 157 (PL-10, PLD-116 (10.0 microg or 10.0 ng/kg; i.g., i.p., i.r.), ranitidine, omeprazole, atropine, methylprednisolone, sulphasalazine (i.p.)] reversed the protracted cysteamine colon injury: the 1 week-regimen (once daily application) started after 1 month post-cysteamine, as well as the 2 weeks-regimen (once daily application), which started after 3 months. The effect on recidive lesion was also tested. These cysteamine lesions may reappear after stopping therapy (after stopping therapy for 3 weeks at the end of 2-weeks regimen started in 3 months-cysteamine female rats) in sulphasalazine group, while this reappearance is markedly antagonized in pentadecapeptide BPC 157 (PL-10, PLD-116)-rats (cysteamine-colon lesion still substantially low).     

Omeprazole and cimetidine in the treatment of ulcers of the body of the stomach: a double blind comparative trial. Danish Omeprazole Study Group.

OBJECTIVE--To see whether omeprazole was superior to cimetidine in healing ulcers of the body of the stomach. DESIGN--Double blind randomised parallel group study of omeprazole versus cimetidine for six weeks with assessment of healing at end of every second week. SETTING--Outpatient referrals in 11 centres in Denmark. PATIENTS--One hundred sixty one patients who satisfied the following criteria: age 18-79; one or more ulcers of body of stomach (that is, at or above the angulus) seen endoscopically within four days before study treatment; no H2 receptor antagonists taken within previous two weeks; no history of gastric surgery and no complications needing surgery; no concurrent treatment or disease that might confound assessment; oral contraception or an intrauterine device being used by women of childbearing age. INTERVENTIONS--Omeprazole 30 mg daily (one capsule in the morning) or cimetidine 1 g daily (one 200 mg tablet thrice daily, two tablets at bedtime) for six weeks. Inactive capsules and tablets provided so that all patients took same number of capsules and tablets daily. Compliance monitored by pill counts. END POINT--Endoscopic evidence of accelerated healing of type I gastric ulcers after four weeks of omeprazole. MEASUREMENTS AND MAIN RESULTS--Pain recorded on diary cards and patients assessed after two, four, and six weeks of treatment for clinical state and by endoscopy and biopsy and repeat laboratory tests. Twenty eight patients withdrawn during trial for violations of protocol. At two weeks healing rates were identical in the two treatment groups (omeprazole 41% (30/73 patients); cimetidine 41% (30/73]. At four weeks cumulative healing rates were 77% (53/69 patients) in the omeprazole treatment group and 58% (41/71) in the cimetidine treatment group (95% confidence interval of difference between groups 4% to 34%). By six weeks the cumulative healing rates in the two treatment groups differed by only 6% (60/68 patients (88%) given omeprazole; 53/65 (82%) given cimetidine). Log rank analysis with ulcer size used as covariable showed a significant difference in healing times in favour of omeprazole. There was no difference in the occurrence of pain relief between the two treatment groups. No serious clinical or biochemical side effects of treatment were noted. CONCLUSIONS--Omeprazole 30 mg daily accelerates healing of ulcers in the body of the stomach as compared with cimetidine 1 g daily. This effect is more pronounced in ulcers greater than 12 mm diameter.     

Hypergastrinaemia evoked by omeprazole stimulates growth of gastric mucosa but not of pancreas or intestines in hamster, guinea pig and chicken

Treatment of chickens, hamsters and guinea-pigs with the long-acting anti-secretagogue omeprazole resulted in elevated levels of serum gastrin. The chickens received 400 mumol/kg by i.m. injection once daily, the hamsters and guinea-pigs received the same dose by the oral route once daily. In all 3 species omeprazole raised the intragastric pH to 4, measured 12-14 h after the administration of the drug. After 10 weeks of treatment, trophic changes were observed in the stomach of hamster and guinea pig and in the proventriculus of chicken. The trophic changes were manifested in a greatly increased stomach weight and gastric mucosal mass. There were no trophic effects outside the stomach (or proventriculus). The results are in agreement with previous observations in the rat and support the view that long-lasting sustained hypergastrinaemia causes trophic changes in the stomach but not in the pancreas or in the intestines.     

Triple therapy with octreotide,galanin, and serotonin reduces the size and blood vessel density and increases apoptosis of a rat colon carcinoma

A rat colonic adenocarcinoma was implanted subcutaneously in female nude (C57BL/6JBom-nu) mice. After 7 days, the animals were divided into different groups. One group received triple therapy with octreotide, galanin, and serotonin, 10 microg/kg body weight of each, twice daily. The second group served as controls and received only saline solution. Three groups received 10 microg/kg body weight twice daily of octreotide, galanin, or serotonin. The last group consisted of controls that received only saline solution. The treatment lasted for 5 days. The tumour volume, wet weight, and relative volume density of blood vessels were significantly decreased after the triple treatment, as compared to controls. Apoptotic index was significantly increased, but the proliferation index was not affected in the group of mice that received triple therapy. There was no significant difference between controls and mice treated with octreotide, galanin, or serotonin regarding tumour volume or weight. The relative volume density of blood vessels was decreased in tumours treated with galanin, but not with octreotide or serotonin. There was no statistical difference in the proliferation index between controls and animals treated with octreotide, galanin, or serotonin, as compared with controls. Tumour necrosis and increased apoptosis may be responsible for the reduction in the volume and weight of the tumour after triple therapy. Tumour necrosis may be caused by the induction of tumour ischemia due to a reduction in tumour blood flow, which is caused by decreased incidence of tumour-feeding blood vessels, and by constriction of tumour-feeding arterioles. These results are promising and may offer treatment for colon cancer.     

Nitric Oxide Synthase Inhibition Promotes Carcinogen-Induced Preneoplastic Changes in the Colon of Rats

l-Arginine is metabolized either to polyamines through arginase and ornithine decarboxylase (ODC) activities or to citrulline and nitric oxide (NO, nitrogen monoxide) through the NO synthase (NOS) pathway. Polyamine levels and ODC activity are high in tumor cells. The aim of this study was to test whether N(G)-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NOS, modulates colon carcinogenesis. Adult male Wistar rats were treated with azoxymethane (AOM, 15 mg/kg ip), a chemical carcinogen, once a week for 2 weeks. One week after the second injection the rats were randomly divided into two groups. One group (n = 8) received l-NAME (10 mg/kg body wt/day) in drinking water. The control group (n = 8) received tap water. After 5 weeks, the rats receiving l-NAME showed enhanced mean basal arterial blood pressure, decreased heart rate, and a significant decrease of the cGMP content in the colonic mucosa. In both groups, AOM induced the formation of colonic aberrant crypt foci (ACF). In l-NAME-treated rats, the number of ACF was higher than in controls by 47%. ODC activity was enhanced by 11-fold. S-Adenosyl-methionine-decarboxylase activity and putrescine concentration were significantly increased in the colonic mucosa of l-NAME-treated rats. The data suggest that l-NAME promotes carcinogen-induced preneoplastic changes in the colon by inhibiting NOS activity and by stimulating polyamine biosynthesis.     

Rat serum antibodies binding to high-molecular-weight glycoprotein(s) on syngeneic colon carcinomas,demonstrated by competition with rat monoclonal antibody

Summary Sera from rats immunized to syngeneic 1,2-dimethylhydrazine colon carcinomas were analyzed for their ability to inhibit the binding of a syngeneic rat IgM monoclonal antibody (10B12) specific for high-molecular-weight glycoprotein(s) from rat colon carcinoma. Immunization with irradiated tumour cells or with tumour tissue extracts resulted in the appearance of a strong inhibiting activity. Sera of animals with established growing tumours and of females shortly after partus also inhibited binding of the monoclonal antibody, while unimmunized animals or animals immunized with irrelevant antigens had no inhibiting antibodies in their sera. Dimethylhydrazinetreated animals showed an increased titer of antibodies binding to the high-molecular-weight glycoprotein, but showed no inhibition of binding of the 10B12 monoclonal antibody. The syngeneic 10B12 rat antibody obviously does not reflect a rare event captured from a hyperimmune animal by the hybridoma technique but rather represents an antibody specificity frequently appearing in the immune response to tumours expressing the high-molecular-weight glycoprotein.     

Antihypertensive effects of Dorstenia psilurus extract in fructose-fed hyperinsulinemic, hypertensive rats.

We examined the effect of methanol/methylene chloride extract of Dorstenia psilurus given by gastric intubation on systolic blood pressure, plasma glucose, insulin, cholesterol, triglycerides and creatinine in rats with fructose-induced hypertension. Male Wistar rats in groups of 6 animals each were fed fructose-rich diets or standard chow for 3 weeks and treated with 100 mg/kg/day or 200 mg/kg/day of plant extract or vehicle for 3 subsequent weeks. Systolic blood pressure was measured every three days using the indirect tail cuff method. Systolic blood pressure was higher in fructose-fed rats (142+/-2 mm Hg, p < 0.01) compared with the controls (112+/-2 mm Hg), and was lower in Dorstenia psilurus-treated groups (127+/-2 and 119+/-1 mm Hg for the dose of 100 and 200 mg/kg, respectively) compared with the fructose-fed rats. Plasma insulin, cholesterol and triglycerides were higher on the fructose-rich diet compared with the controls. Plasma insulin and cholesterol were lower in the Dorstenia psilurus-treated groups. These results suggest that, Dorstenia psilurus treatment could prevent and reverse high blood pressure induced by a diet rich in fructose probably by improvement of plasma insulin levels. The plant extract might prove useful in the treatment and/or prevention of hypertension.     

Effect of cimetidine, ranitidine and omeprazole on postprandial gastrin and somatostatin release in conscious dogs

During a first series of experiments, the gastrin responses to a meal were measured and compared to the responses seen after administration of cimetidine (2.5 mg/kg/h) or omeprazole (2 mg/kg). During a second series of experiments the effects of cimetidine (2.5 mg/kg/h), ranitidine (0.5 mg/kg/h) and omeprazole (2 mg/kg) on post-prandial gastrin and somatostatin release were determined in experiments during which the intragastric pH was maintained close to 6.4. During a third series of experiments, the effects of cimetidine (2.5 mg/kg/h) and omeprazole (2 mg/kg) on basal gastrin and somatostatin release were estimated. Postprandial gastrin release was increased by cimetidine and by omeprazole. When acidification of the gastric content was prevented by intragastric titration, postprandial gastrin release was increased by about 100%. No further increase was observed when the animals were concomitantly treated with cimetidine, ranitidine or omeprazole. Intragastric titration did not alter postprandial somatostatin release. Concomitant administration of H2 blockers decreased the somatostatin response to the meal, while concomitant administration of omeprazole did not alter this release. No significant changes were observed in basal gastrin or somatostatin levels after administration of cimetidine or omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS)     

Starvation-induced suppression of pituitary-testicular function in rats is reversed by pulsatile gonadotropin-releasing hormone substitution

This study was carried out to test the hypothesis that reduced hypothalamic GnRH release is responsible for the suppression of reproductive functions during starvation. Adult male rats were kept for 4 days under total fasting (only water allowed) and injected during this time at 2-h intervals with 100 or 500 ng/kg BW of GnRH or vehicle. Serum levels of LH and FSH decreased by 30% during starvation (p less than 0.05), and these effects were fully reversed by either dose of GnRH treatment. Starvation reduced the pituitary mRNA contents of the gonadotropin common alpha- and FSH beta-subunits by 30% and 35% in starved animals (p less than 0.05 for both), but the LH beta-subunit mRNA was unaffected. The GnRH treatments partly or totally reversed these changes, but up-regulation of the mRNA levels by GnRH was seen only in controls fed ad libitum. Starvation reduced the testicular and serum levels of testosterone by 84% (p less than 0.01) and 42% (p less than 0.05), respectively. These changes were fully reversed by the 500-ng/kg dose of GnRH treatment during fasting, but only serum T was completely reversed by the 100-ng/kg GnRH treatment. To elucidate whether fasting per se had direct effects at the gonadal level, we blocked the secretion of gonadotropins by treatment with a GnRH antagonist, and replaced the gonadotropins by injecting of hCG (10 IU/kg BW once daily) and hFSH (75 IU/kg BW once daily). No differences were observed between starved and control animals in either testicular or serum levels of T, or in accessory sex gland weights.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of melatonin on glycoprotein levels and oxidative liver injury in experimental diabetes

In this present study, the duration of melatonin (Mel) administered to diabetic rats was prolonged so as to examine its effects on the biochemical liver parameters of diabetic rats. In the experiment, Male Sprague Dawley rats were divided randomly into five groups; the control, diabetic + Mel, diabetic, diabetic + insulin, and diabetic + Mel + insulin. Diabetes mellitus was induced by administration of a single dose of streptozotocin (60 mg/kg) intraperitoneally and rats were given vehicle as a solvent for Mel every day for 12 weeks. In the diabetic + Mel group, diabetic rats were administered Mel (10 mg/kg/day) for 12 weeks to treat diabetes. The diabetic + insulin group were diabetic rats given insulin (6 U/kg) subcutaneously for 12 weeks. The diabetic + Mel + insulin rats received insulin and Mel at the same dose and time. At the end of the experiment, the animals were decapitated and liver tissues were taken. The protective effect of Mel on liver tissue of diabetic rats was investigated, total antioxidant status, total oxidant status, reactive oxygen species, oxidative stress index, adenosine deaminase, xanthine oxidase, paraoxonase 1, sodium/potassium ATPase, myeloperoxidase, γ-glutamyl transferase, sorbitol dehydrogenase, tumor necrosis factor-alpha, homocysteine, nitric oxide, glucose-6-phosphate dehydrogenase, and glycoprotein levels were determined in liver tissues. Treatment with Mel and/or insulin has been found to have a protective effect on biochemical parameters. The results showed that administration of Mel to diabetic rats prevented the distortion of the studied biochemical parameters of liver tissues.     

Stimulating effect of pentagastrin on cancer cell proliferation kinetics in chemically induced colon cancer in rats

Pharmacological doses of pentagastrin or gastrin are known to stimulate cell proliferation in normal colonic epithelium but the growth-promoting effect of gastrin on colon carcinoma is still controversial. In this study morphological parameters were measured to study the effect of pentagastrin (240 micrograms/kg) on the cell proliferation kinetics in experimental tumours. Colon cancer was produced in rats by weekly injections (20 mg/kg b.wt.) of 1.2-dimethylhydrazine for 24 weeks. Tritiated thymidine was given after administration of pentagastrin or the control solution to the animals. 75% of the animals from the pentagastrin group and 66% of the controls had at least one colon cancer. Autoradiographs of the colonic tumors were performed and the percentage of labeled cells in the cancer cell population was determined after counting 4000 to 16,000 cancer cells per tumor. The labeling index for cancer cells in the pentagastrin-treated group (21.49 +/- 1.76%) was higher (P less than 0.01) than in the control group (14.76 +/- 0.66%). In a second study vincristine sulphate (1 mg/kg) was given to the animals 20 h after administering pentagastrin or the control solution. The percentage of arrested metaphases in the tumours was determined after counting 10,000 to 24,000 cancer cells per histological section. Pentagastrin increased (P less than 0.01) the mean metaphase index by 108% (4.9 +/- 0.44% vs 2.35 +/- 0.32%). These data indicate that cell cycle manipulation of colon cancer is possible with hormonal peptides.     

Alteration of macromolecular events and elemental levels in the skin of UVC exposed hairless mice

Swiss mice (S/RV/Cri-ba) were exposed to a spectral range of UV light emitting predominantly lambda 253.7 nm. Following a cumulative dose of 22.5 X 10(3) KJ/m2 tumours were induced. The tumour development occurred after 52 weeks, relatively a longer time interval following exposure, compared with shorter time intervals required for production of tumours in mice by spectral range UVA and UVB as observed by other workers. A study of biochemical events viz. levels of protein, DNA, zinc, iron, sodium and potassium has been made in the skin samples of control and irradiated animals following ultraviolet irradiation with a dose of 22.5 X 10(3) KJ/m2. Study of macromolecular events in the skin of control and irradiated mice, showed fluctuations in the levels of DNA. A particularly notable event is the occurrence of increased levels of DNA and zinc and their persistence during the 9-39 weeks post UV interval prior to tumour production. No such variation was observed in the control group in any of the intervals. Increased levels were also seen in case of iron, sodium and potassium at different intervals in the post UV periods. These fluctuations in various biochemical events are deemed to be indicative of UV initiated biochemical changes.