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PubMed2006

Angiogenesis pattern of native and cross-linked collagen membranes: an immunohistochemical study in the rat.

The aim of the present study was to immunohistochemically evaluate angiogenesis pattern of native and cross-linked collagen membranes after subcutaneous implantation in rats. Five commercially available and three experimental membranes (VN) were included: (1) BioGide (BG), (2) BioMend (BM), (3) BioMend Extend (BME), (4) Ossix (OS), (5) TutoDent (TD), and (6-8) VN(1-3). Specimens were randomly allocated in unconnected subcutaneous pouches (n=4) separated surgically on the back of 40 wistar rats, which were divided into five groups (2, 4, 8, 16, and 24 weeks), including eight animals each. Pattern of angiogenesis was labelled using primary mouse monoclonal antibody to transglutaminase II. For each membrane, the period of time, needed for a complete and homogeneous transmembraneous vascularization, was assessed immunohistomorhometrically. Differences between the membranes were found regarding the initial pattern of transmembraneous angiogenesis, as evaluated 2 weeks following implantation. Mean cross- and longitudinal-sectional area of blood vessels (%) was highest for VN(3) (5.27+/-2.73), followed by BG (2.45+/-0.88), VN(1) (2.07+/-0.29), VN(2) (1.91+/-0.55), TD (1.44+/-0.53), BME (0.35+/-0.29) and BM (0.25+/-0.4). In contrast to BG and VN(1-3), BM, BME and TD exhibited a homogeneous transmembraneous formation of blood vessels merely 4-8 weeks following implantation. OS, however, exhibited no signs of angiogenesis throughout the whole study period. Within the limits of the present study, it may be concluded that pattern of transmembraneous angiogenesis markedly differs among the membranes investigated.

Animals↗

PubMed1995

Effect of dextran and enoxaparin on early ePTFE graft thrombogenicity in sheep.

OBJECTIVES: To evaluate the effect of low molecular weight heparin (LMWH), dextran 70 and their combination on platelet adhesion and fibrinogen uptake in ePTFE grafts in an experimental sheep model. DESIGN: Prospective open study. SETTING: Animal Laboratory of a University Hospital. MATERIALS: Early thrombogenicity of ePTFE grafts was studied after interposition in the two common carotid arteries of 40 adult sheep. The animals received one of four different treatment regimens in a double blind randomised way: enoxaparin and polygeline, saline and dextran 70, enoxaparin and dextran 70 or saline and polygeline (control). The substances were administered i.v. with a total dose of 73 antifactor-Xa U/kg for enoxaparin and 1.0 g/kg for dextran 70. Polygeline and saline were used as placebo substances in equivalent volumes. On one side (random allocation) the carotid blood flow was restricted to 25 ml/min, on the other side it was left unrestricted. CHIEF OUTCOME MEASURES: The following variables were studied: 1) fibrinogen uptake; 2) platelet uptake; 3) early graft patency; 4) blood flow in patient grafts; 5) visible presence of graft thrombus; 6) thrombus weight. MAIN RESULTS: The results verified the importance of adequate blood flow as only 30% of grafts with restricted blood flow in the control group were patent compared with 80% of those with unrestricted blood flow (p = 0.038). Dextran 70, enoxaparin and the combination of the two increased early graft patency (p < 0.05) and reduced thrombus weights (p < 0.05) in grafts with restricted blood flow. The relative number of grafts with thrombus free surface was increased in the unrestricted blood flow situation. CONCLUSIONS: Dextran 70 and enoxaparin appeared to be equally effective in decreasing fibrinogen and platelet uptake in the grafts. Their combination was not significantly more effective although there was a favourable trend.

Animals↗

PubMed1987

Assessment of an oxfendazole pulsed release bolus for control of parasitic gastroenteritis in calves in a rotational grazing system.

A group of 71 Friesian bullocks, aged six to nine months, vaccinated against lungworm, were randomly allocated on a liveweight basis to two groups of 40 and 31 animals. At turn-out each calf in the group of 40 calves was dosed orally with a pulsed release bolus designed to deliver five doses of oxfendazole at regular intervals during a period of up to 130 days, the first dose being released about 21 days after administration. The group treated with the bolus grazed 2.4 ha and the control group grazed 3.6 ha of permanent pasture for six weeks before having additional access to similar areas of silage aftermath. The control group was treated 99 days after turn-out and when they were housed with fenbendazole (7.5 mg/kg). Faecal worm egg counts, plasma pepsinogen activities, pasture larval counts and liveweights were recorded fortnightly. Significant reductions in worm egg counts and plasma pepsinogen activities were recorded in the calves dosed with the pulsed release bolus together with significant improvements in the liveweight of younger calves compared with control animals. Pasture larval counts were lower in the fields grazed by animals treated with the bolus.

Animals↗

PubMed1992

Co-culture of in vitro fertilized bovine embryos with different cell monolayers.

The effects of different cell monolayers on in vitro development of early bovine embryos derived from in vitro maturation and fertilization were examined in this study. Early embryos (four to eight cells) were randomly allocated to bovine granulosa cell (GC), oviductal cell (OC), or uterine cell (UC) monolayers in Exp. 1 and to GC, skin cell (SC; from 10-d-old chicken embryos), testicular cell (TC; from 10-d-old mouse), and liver cell (LC; from 10-d-old chicken embryos) monolayers in Exp. 2, and cultured for 6 d at 38.6 degrees C in a humidified atmosphere of 5% CO2 in air. The culture medium was 12.5 mM HEPES TCM 199 supplemented with 1% calf serum and 1 mM sodium pyruvate. In Exp. 1, the percentage of four- to eight-cell embryos that developed to blastocysts on GC, OC, and UC monolayers was 26.9 (28/104), 37.5 (39/104), and 39.2 (40/102), respectively. In Exp. 2, the percentage of four- to eight-cell embryos that developed to blastocysts on GC, SC, TC, and LC monolayers was 53.3 (40/75), 42.9 (33/77), 49.3 (37/75), and 44.3 (35/79), respectively. There were no significant differences in development among groups in either experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

Influence of cytotoxic agents on intraperitoneal tumor implantation after laparoscopy.

PURPOSE: Recent experimental studies suggest that laparoscopic surgery for abdominal malignancy may be associated with increased tumor implantation. This study investigated the influence of cytotoxic agents (administered intraperitoneally or intramuscularly) on implantation of a tumor cell suspension after laparoscopic surgery in an experimental model. METHODS: Thirty-three Dark Agouti rats underwent laparoscopy with CO2 insufflation and instillation of a tumor cell suspension into the abdominal cavity. Rats were randomly allocated to one of the following study groups (9 rats in the control group, 6 rats in all other groups): 1) control (no intraperitoneal instillation); 2) intraperitoneal normal saline (0.9 percent); 3) intraperitoneal povidone-iodine (Betadine to normal saline 1:10 dilution); 4) intraperitoneal methotrexate (2 doses of 0.125 mg/kg body weight in normal saline administered 24 hours apart); 5) intramuscular injection of 2 doses of 0.125 mg/kg body weight administered 24 hours apart (no intraperitoneal agent). Rats were killed 7 days after the procedure, and the peritoneal cavity and port sites were examined for the presence of tumor. RESULTS: A significant reduction in tumor implantation and port-site metastases was observed in all treatment groups (povidone-iodine and intramuscular and intraperitoneal methotrexate). CONCLUSIONS: This study suggests that tumor implantation after laparoscopic surgery and port-site metastases might be prevented by the intraperitoneal or systemic administration of cytotoxic agents. Further studies are needed to determine whether these findings can be applied to clinical practice.

Animals↗

PubMed1994

Effect of methylprednisolone on angiogenesis in syngeneic rat tracheal grafts.

Airway anastomotic complications remain a cause of morbidity after clinical lung transplantation. The use of corticosteroid therapy to control pulmonary rejection has raised concern over delayed airway healing. We therefore investigated the hypothesis that the effects of methylprednisolone (MP) impair the revascularization and epithelial regeneration of heterotopic syngeneic tracheal isografts. Lewis rat tracheal segments were wrapped in omentum and implanted in the abdomen of recipient rats. All recipients received cyclosporin A (CsA) (5 mg.kg-1.day-1) and were randomly allocated into three groups of 12 rats each according to the daily MP dose: group II, no MP; group III, 1 mg.kg-1.day-1; and group IV, 2 mg.kg-1.day-1. In each group, 6 animals were sacrificed after 7 and 14 days. Normal, untreated rats served as controls (group I). Epithelial regeneration was assessed histologically by a blinded subjective scoring system and by measurement of epithelial thickness. Tracheal revascularization was quantitated in terms of the number of blood vessels per square millimeter of tracheal wall and the vessel area was quantitated in terms of the percentage of the tracheal wall area. In animals treated with MP and CsA, the trachea exhibited significantly better regeneration after 14 days than it did in animals treated only with CsA. Epithelial regeneration was improved between 7 and 14 days in the groups treated with MP (group III, p = 0.01; group IV, p = 0.04). The epithelial thickness for all three study groups was significantly greater than that in the control group and returned toward normal after 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

The effects of cisplatinum and vincristine on peripheral nerve regeneration.

Current treatment modalities for extremity sarcoma often include tumor extirpation plus neoadjuvant therapy. Limb-sparing surgery may require reconstruction of critical nerve defects. Neurotoxic side effects from adjuvant chemotherapy have been reported and raise concerns regarding the effects of chemotherapy on nerve regeneration. In an attempt to define the effects of adjuvant chemotherapy on peripheral nerve regeneration, cisplatin and vincristine were administered to rats following isografting of the posterior tibial nerve. Parameters used to assess peripheral nerve regeneration included walking track analysis and histomorphology. Sixty 250-g Sprague-Dawley rats were randomly allocated into one of three treatment groups. Each animal underwent a 15-mm reversed interposition nerve isograft from 30 donor rats into the right posterior tibial nerve. Ten animals served as control. The remaining animals were divided into two groups of 25 animals each. One group received cisplatin (75 mg/m2) and the other group received vincristine (1 mg/m2). Chemotherapy was administered at 4-week cycles for a total of six cycles (24 weeks). Walking track analysis was performed monthly. Nerve specimens were harvested from the grafted segment and the distal posterior tibial nerve for histomorphology. Walking track analysis demonstrated no statistical difference in print length between the control and chemotherapeutic groups at the conclusion of the study. The number of axons per square millimeter and nerve fiber density were not statistically different between control and chemotherapeutic groups. In the rodent posterior tibial nerve model, postoperative adjuvant therapy does not significantly alter functional outcome in peripheral nerve regeneration. The practice of immediate nerve grafting after tumor extirpation, despite planned postoperative chemotherapy, is supported.

Animals↗

PubMed2001

[Imitative restenosis after percutaneous transluminal coronary angioplasty prevented by buyang huanwu decoction in rabbits].

OBJECTIVE: To examine the preventive effect of Buyang Huanwu Decoction (BYHWD) on imitative restenosis after percutaneous transluminal coronary angioplasty (PTCA) in diet-induced atherosclerotic rabbits. METHODS: Diet-induced atherosclerotic rabbits were randomly allocated into group 1 (n = 24, fed with BYHWD one week before and 4 weeks after the operation, 2 ml/kg per day, containing herbal drug 8.4 g/ml) and group 2 (n = 20, as control). Balloon angioplasty was performed in the abdominal arota to mimic coronary angioplasty. RESULTS: Sixty days after operation: (1) Incidence of hyperplasia of the intima was 7/24 (29.2%) in group 1 vs 17/20 (85.0%) in group 2, P < 0.01; (2) Comparison of area of hyperplastic intima was (0.54 +/- 0.21) mm2 vs (1.67 +/- 0.75) mm2, P < 0.01; (3) Area of hyperplastic intima/area of lumen (limited by the internal elastic membrane was (18.0 +/- 7.2)% vs (56.0 +/- 17.1)%, P < 0.01; (4) Intact lumen/dilated lumen was (0.74 +/- 0.03) vs (0.35 +/- 0.07), P < 0.01; (5) Effect of serum taken from group 1 on cultured smooth muscle cells showed by 3H-TdR method was (4110.14 +/- 1977.01) cpm, which was significantly less than that of serum taken from group 2 [(7960.14 +/- 2802.59) cpm, P < 0.05]. CONCLUSION: BYHWD has significant preventive effect on the imitative post PTCA restenosis in diet-induced atherosclerotic rabbits.

Angioplasty, Balloon, Coronary↗

PubMed1991

[Subchronic oral toxicity study of cyanoguanidine in F344 rats].

A 13-week subchronic oral toxicity study of cyanoguanidine was performed in male and female F344 rats by feeding of CRF1 powder diets containing 0, 1.25, 2.5, 5 and 10% cyanoguanidine to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. The rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Inhibition of body weight gain was more marked in both sexes of the 10% group and in females of the 5% group as compared with the control group. Mean food intake in males of the groups treated with 5% or 10% and in females of the 10% group was significantly higher than that in the control group. Serum biochemical investigation revealed a higher level of serum BUN in both sexes of the 10% group. On histopathological examination, toxic changes characterized by the occurrence of intranuclear eosinophilic inclusion bodies in the proximal tubular epithelium of the kidney were observed in both sexes of the 10% group. Similar inclusion bodies were also seen in 2 out of 10 males of the 5% group. From these results, it was concluded that a level of 10% of cyanoguanidine in the diet is unequivocally toxic. A dose level, 5% cyanoguanidine, in the diet might be appropriate as a high dose for a carcinogenicity study.

Administration, Oral↗

PubMed1989

The performance of the two-stage analysis of two-treatment, two-period crossover trials.

In the two-treatment, two-period crossover trial, patients are randomly allocated either to one group that receives treatment A followed by treatment B, or to another group that receives the treatments in the reverse order. Grizzle first proposed a two-stage procedure for analysing the data from such a trial. This paper examines the long-run sampling properties of this procedure, in terms of mean square error of point estimates, coverage probability of confidence intervals and actual significance level of hypothesis tests for the differences between the effects of the two treatments. The advantages of incorporating baseline observations into the analysis are also explored. Because the preliminary test for carryover is highly correlated with the analysis of data from the first period only, actual significance levels are higher than nominal levels even when there is no differential carryover. When carryover is present, the nominal level very seriously understates the actual level, and this becomes even worse when baseline observations are ignored. Increasing sample size only exacerbates the problem since this adverse behaviour then occurs at smaller values of the carryover effect. It is concluded that the two-stage analysis is too potentially misleading to be of practical use.

Analysis of Variance↗

PubMed1996

Neural involvement in post-traumatic osteopenia: an experimental study in the rat.

The effect of sciatic nerve resection on post-traumatic bone loss and mechanical strength of the ipsilateral (IL) and contralateral (CL) femoral shafts and necks was studied 25 days after a tibial fracture. We subjected 45 male rats to a standardized tibial fracture, stabilized it with a modular intramedullary nail and then randomly allocated the animals to two groups: right sciatic nerve resection (SNR group) or sham operation (sham group). All of the operated hindlimbs were further immobilized in a plaster cast to avoid unequal loadbearing between the two groups. After 25 days of healing, 85Sr incorporation in the IL femora was 10% lower in the SNR group compared to the sham group, indicating a lower bone mineralization after sciatic nerve resection. The bone mineral content was 15% higher in the SNR group ipsilaterally. Accordingly, the bending moment and energy absorption in the femoral midshaft were higher in the SNR group compared to the sham group. The sciatic nerve resection protected the femoral shaft against the normally occurring post-traumatic bone loss after a tibial fracture. This protective effect of the neurectomy also occurred in the femoral neck, but not to the same extent. A protective effect was also present in the CL femur, suggesting additional systemic effects of the sciatic nerve resection.

Absorptiometry, Photon↗

PubMed2006

Effects of dexamethasone treatment (to mimic stress) and Vitamin E oral supplementation on the spermiogram and on seminal plasma spontaneous lipid peroxidation and antioxidant enzyme activities in dogs.

The objective was to determine if treatment with dexamethasone (to mimic stress) has a deleterious effect on the spermiogram and on the composition of seminal plasma in the dog and whether adverse effects were reduced by oral supplementation with Vitamin E. Eighteen adult male Rottweiler dogs were randomly allocated in a 2 x 2 factorial treatment design (with or without dexamethasone treatment versus with or without Vitamin E supplementation). Dogs in the supplemented group received 500 mg of alpha-tocopherol (Vitamin E)/dog/day per os for 10 weeks. Dexamethasone (0.01 mg/kg/day i.m.) was given once daily for 7 days, starting 7 days after the onset of Vitamin E supplementation. Food intake, body condition score and body weight were assessed daily. Semen collections (digital manipulation) were performed twice weekly for 14 weeks and blood samples (for plasma concentrations of cortisol and testosterone) were collected once a week. Dexamethasone treatment significantly reduced ejaculate volume and increased thiobarbituric acid-reactive substances (TBARS) in the seminal plasma. In contrast, supplementation with Vitamin E increased sperm motility, vigor and concentration and decreased the percentage of major sperm defects. In conclusion, dexamethasone treatment (to mimic stress) had a deleterious effect on the spermiogram and on the seminal plasma lipid peroxidation in dogs; however, some of these effects were prevented by oral supplementation with Vitamin E.

Animals↗

PubMed1994

Is endotoxin-induced hypotension related to nitric oxide formation?

Nitric oxide (NO), an endothelium-derived relaxing factor (EDRF), is released by different types of cells under the influence of endotoxin and various cytokines: a causative role of endothelium-derived NO in the endotoxin-induced hypotension has thus been suggested. To test the hypothesis that NO may be involved in the acute hypotension following endotoxin challenge, we administered a competitive inhibitor of NO synthase, L-N-monomethylarginine (L-NMMA) to anesthetized dogs in the presence and absence of endotoxin. Dogs were randomly allocated to three groups. Group 1 (n = 3) was given Escherichia coli endotoxin (3 mg/kg, i.v.), group 2 (n = 3) was given L-NMMA (5 mg/kg, i.v. bolus) 15 min after endotoxin and group 3 (n = 3) was given L-NMMA only. One additional dog was given L-arginine (100 mg/kg, i.v. bolus) after L-NMMA and endotoxin to reverse the inhibition of NO synthase. In each animal, saline was infused intravenously throughout the experiment to restore and maintain pulmonary artery occluded pressure at baseline level. After L-NMMA, the increases in mean arterial pressure were similar in group 2 (from 55 +/- 18 to 75 +/- 15 mm Hg, p < 0.01) and in group 3 (from 107 +/- 27 to 128 +/- 24 mm Hg, p < 0.01). Systemic vascular resistance increased from 2,994 +/- 72 to 3,658 +/- 673 dyn.s.cm-5 (p < 0.01) in group 3. Group 1 had lower plasma lactate levels than group 2 (3.5 +/- 2.3 +/- vs. 2.0 +/- 1.6 mEq/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

PubMed1999

[Influences of gestational hyperglycemia on the function of fetal rat pancreatic islets].

OBJECTIVE: To investigate the influences of gestational hyperglycemia on the function of fetal rat pancreatic islets. METHODS: Twenty-eight pregnant SD rats were randomly allocated into two groups. The study group was continually infused with 30% glucose at the rate of 2 ml/min, while the controls with sterilized distilled water in the same time and at the same rate. The infusion began on day 16.5 post-coitus and lasted for 5 days until the removal of the fetuses. The functions of the beta-cells in fetal rat islets were studied by determining the content of insulin, using the tests of extracting, releasing and perfusing. RESULTS: The data showed that the insulin content of study group (3,329.81 +/- 163.39) ng was significantly higher than that of controls (2,390.04 +/- 151.39) ng (P < 0.05); After 2 hours' incubation in Hanks solution which contained different concentration of glucose, increased insulin secretion was found in the study group (P < 0.05); When the islets were perfused, the insulin peak value of study group was higher and appeared earlier than that of controls. CONCLUSION: Insulin synthesis and secretion function of beta-cells of fetal pancreas from hyperglycemia rats were enhanced and the pancreas had a hypersensitive response to glucose challenge.

Animals↗

PubMed1998

Comparison of apical leakage shown by four different dyes with two evaluating methods.

A study was conducted in vitro to assess and compare the extent of apical leakage of four dyes by two commonly-used evaluation methods. For the study, 120 single-rooted extracted teeth were prepared by the step-back technique and obturated by lateral condensation with gutta-percha and Roth 801 sealer. After randomly allocating the roots into six groups, they were immediately immersed in dye for 72 h, using vacuum for 30 min at 40 degrees C. Teeth were immersed in Eosin, Methylene Blue, Black India Ink and Procion Brilliant Blue and cross-sectioned in 0.7 mm thick slices. Those immersed in Black India Ink and Procion Brilliant Blue were also evaluated by the clearing process. Dye penetration was assessed using a stereomicroscope. A statistically significant greater dye penetration was measured in the cross-sectioned group compared to the clearing group using the same dyes (Black India Ink, P = 0.020, Procion Brilliant Blue, P = 0.040). In the cross-section groups, no statistical significant difference was observed in the amount of leakage comparing the four dyes. No statistically significant difference was found in the leakage pattern of Procion Brilliant Blue and Black India Ink using the clearing technique (P = 0.797). The evaluating method (cross-sections versus clearing) rather than the dye properties was the main difference between results. More research is needed to standardize dye leakage studies.

Carbon↗

PubMed2005

The effects of XeCl laser etching of Ni-Cr alloy on bond strengths to composite resin: a comparison with sandblasting procedures.

OBJECTIVES: The aim of this study was to determine the effect of laser surface treatment of Ni-Cr alloy on the tensile bond strength of a proprietary composite resin (Panavia 21) in comparison with a conventional sandblasting technique. METHODS: Eighty cylinders of Ni-Cr were randomly allocated into the following groups: Group I-sandblasting only; Group II-low laser fluence (3.0 J/cm(2)); Group III-medium laser fluence (4.0 J/cm(2)); Group IV-high laser fluence (4.9 J/cm(2)); Group V-sandblasting in combination with medium laser fluence (4.0 J/cm(2)). Specimens within groups were bonded into pairs with resin cement as per manufacturer's instructions. They were then de-bonded using a tensile test. RESULTS: The mean de-bond strengths (SD) were: Group I-13.1 (4.2)MPa; Group II-17.6 (5.8)MPa; Group III-25.7 (11.8)MPa; Group IV-22.6 (6.6)MPa; Group V-41.8 (13.2)MPa. A statistically significant improvement (Bonferroni, p<0.05) in bond strength was found for the specimens which had been both lased and sandblasted (Group V) compared to all other groups, including those which were only sandblasted. SIGNIFICANCE: Laser pre-treatment of Ni-Cr alloy increases bond strength to composite resin compared with sandblasting; laser pre-treatment in combination with sandblasting further increases the de-bond strengths.

Chlorides↗

PubMed2003

Effect of alendronate on bone ingrowth into porous tantalum and carbon fiber interbody devices: an experimental study on spinal fusion in pigs.

Recent studies have reported that bisphosphonates reduce the resorption of grafted bone and inhibit bone resorption at a bone-implant interface. However, it is not known whether bisphosphonates affect bone ingrowth into porous biomaterial or spine fusion interbody devices with an autograft. In this study, 18 pigs (9 in each group) underwent anterior intervertebral lumbar arthrodeses at L2-3, L4-5 and L6-7. Each level was randomly allocated to one of the 3 implants: a solid piece of porous tantalum (Hedrocel), a porous tantalum ring or a carbon fiber cage both packed with an autograft. Alendronate was given orally to one of the groups. The radiographic and histological findings in the two groups 3 months after operation were similar in these devices. Histological examination showed that the original graft was entirely replaced by new trabecular bone in both groups. On histomorphometric analysis, the bone volume fraction, both inside the central hole of porous tantalum ring and in the porous tantalum, was larger in the pigs given alendronate than in the controls, but the fraction inside and around the central hole of the carbon fiber cage was not affected by this treatment. Short-term alendronate treatment, in a relatively low dose, does not impair the formation of new bone, but increases bone ingrowth into the central hole of the porous tantalum ring and the pores of the porous tantalum in this porcine model. This may be an effective way to enhance early biologic fixation of porous intervertebral implants.

Alendronate↗

PubMed1992

Promotion of aberrant crypt foci and cancer in rat colon by thermolyzed protein.

BACKGROUND: We have previously shown that thermolyzed protein (casein) cooked with fat in the diet of the rat promotes the growth of aberrant crypt foci (putative precursors of colon cancer) assessed at 100 days. PURPOSE: To determine how thermolysis affects this promotion, we examined thermolysis conditions, quantity of thermolyzed protein in the diet, and duration of thermolysis. To determine whether the previous finding of promotion of aberrant crypt foci corresponds to promotion of cancers assessed much later, we carried out promotion studies until colon cancers appeared. METHODS: F344 rats were given an initiating dose of azoxymethane and were then randomly allocated to groups receiving diets differing in their quantity and quality of casein. The groups were examined for aberrant crypt foci and tumors in the colon. RESULTS: Aberrant crypt foci were promoted by diets containing thermolyzed casein (180 degrees C, 2 hours). Promotion increased with increasing level of thermolyzed casein in the diet (to 20%) and with increasing thermolysis time (to 4 hours). The number of animals with polyps and cancers was higher in the animals receiving thermolyzed protein (2 hours), 16/23 versus 9/26 (P less than .05) and 10/26 versus 3/27 (P less than .05), respectively. The number of aberrant crypts per focus and the number of large aberrant crypt foci were higher in the tumor-bearing animals. CONCLUSIONS: Thermolyzed casein promotes early colonic precursor lesions in a dose-dependent and thermolysis time-dependent manner; thermolyzed casein also promotes colon cancer. IMPLICATIONS: The promoter formed on thermolysis could be involved in colon cancers associated with diets cooked at elevated temperatures, such as can occur with high-fat diets.

Animals↗