Ficus dubia latex extract prevent DMH-induced rat early colorectal carcinogenesis through the regulation of xenobiotic metabolism, inflammation, cell proliferation and apoptosis.

Ficus dubia latex is recognized as a remedy in Asian traditional medicine with various therapeutic effects. The present study aimed to determine the preventive action of Ficus dubia latex extract (FDLE) on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis and its mechanisms. The experiment included an initiation model in which rats were orally administered with FDLE daily for 1 week before DMH injection until the end of the experiment, while only after DMH injection until the end in the post-initiation model. The results firstly indicated that FDLE treatment could reduce the level of methylazoxymethanol (MAM) in rat colonic lumen by inhibition of the activities of both phase I xenobiotic metabolizing enzymes in the liver and ß-glucuronidase in the colon, leading to reduced DNA methylation in colonic mucosal cells, related to the number of ACF in the initiation stage. Besides, FDLE modulated the inflammation which could suppress the growth and induce apoptosis of aberrant colonic mucosal cells, leading to retardation of ACF multiplicity. Therefore, FDLE showed the ability to suppress the DMH-induced rat ACF formation and inflammation promoted growth of ACF. In conclusion, FDLE had the potential to prevent carcinogens-induced rat colorectal carcinogenesis in the initiation stage.

Antioxidant and Anticarcinogenic Potentials of Propolis for Dimethylhydrazine-Induced Colorectal Cancer in Wistar Rats.

Propolis is a natural compound with anticarcinogenic properties. The present study aimed to compare the inhibitory effect of ethanolic extract of propolis (EEP) and vitamin E on dimethylhydrazine-induced colon lesions in rats. In this study, 60 rats were randomly categorized into six 10-member groups. After 13 weeks, blood and colon tissue were sampled to examine some factors. The parameters included red (RBC) and white (WBC) blood cell profile, lactate dehydrogenase (LDH), C-reactive protein (CRP), total protein (TP), creatine kinase (CPK), and albumin, as well as the extent of colon histological lesions, protein expression (adenomatous polyposis coli (APC), proliferating cell nuclear antigen (PCNA), carcinoembryonic antigen (CEA), and platelet-derived growth factor (PDGF)), and oxidative stress markers (total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD)) in colon tissue. A significant decrease was observed in congestion, mitotic index, inflammation, and cell destruction in colon tissue in dimethylhydrazine group in comparison with the control group (P < 0.05). The EEP exposed rats exhibited a significant lower oxidative stress than the DMH group (P < 0.05). Furthermore, the extract significantly affected TAC level (P < 0.05). While the expression level of APC rose substantially in the EEP-treated group compared to the DMH group, the level of PCNA, CEA, and PDGF proteins significantly reduced. It seems that the EEP can efficiently prevent DMH-induced colonic lesions. Furthermore, its effectiveness is more than the vitamin E, which is a strong antioxidant.

5-fluorouracil and curcumin with pectin coating as a treatment regimen for titanium dioxide with dimethylhydrazine-induced colon cancer model.

Colorectal cancer was inducted in Wister rats using titanium dioxide nanoparticles (TiO2NPs) and dimethylhydrazine (DMH) and treatment using 5-fluorouracil (5-FU) and curcumin (CUR), individually and following a synergistic approach. Compatibility studies are evaluated by using FT-IR spectra analysis, and Vero cell lines as well as HCT-116 cell lines are used for evaluating the synergistic approach. It was then followed by induction of colorectal cancer in rats for 70 days and treatment using 5-FU and CUR with pectin coating (individually and in combination) for 28 days. The reports state that 5-FU and CUR combination was found to be compatible. The synergistic effect was evaluated for1:1, 1:2, 1:4, and 2:1 ratio of 5-FU:CUR, where 1:4 ratio shows a CI50 value of 0.853, selected further for the animal studies. The 1:4 ratio of 5-FU and CUR (50:200) shows to be effective for the treatment of colorectal cancer within 28 days, proven using histopathology report, bodyweight analysis, and hematological reports. 5-FU and CUR (1:4) ratio with pectin coating was proven effective for the treatment of colorectal cancer induced by TiO2NPs with DMH and was found to produce a synergistic effect.

Styrax camporum, a typical species of the Brazilian cerrado, attenuates DNA damage, preneoplastic lesions and oxidative stress in experimental rat colon carcinogenesis.

Styrax camporum Pohl, a typical species from the Brazilian cerrado, commonly known as "benjoeiro", is used to treat gastroduodenal diseases. In previous studies carried out by our research group, hydroalcoholic extract of S. camporum stems (SCHE) exhibited antigenotoxic and antiproliferative effects. For a comparative analysis of the chemopreventive effect of SCHE, the aim of this study was to investigate the influence of SCHE against carcinogen 1,2-dimethylhydrazine (DMH)-induced DNA damage and pre-neoplastic lesions in Wistar rat colon. Animals were treated orally with SCHE at 250, 500 or 1000 mg/kg body weight in conjunction with a subcutaneous injection of DMH. DNA damage was assessed using the comet assay while tpre-neoplastic lesions by aberrant crypt foci (ACF) assay. The following hepatic oxidative stress markers were determined including activities of catalase (CAT) and glutathione S-transferase (GST) as well as levels of reduced glutathione (GSH) and malondialdehyde (MDA). Treatment with SCHE was not genotoxic or carcinogenic at the highest dose tested (1000 mg/kg b.w.). The extract effectively inhibited DNA damage and pre-neoplastic lesions induced by DMH administration at all concentrations tested. Measurement of CAT, and GST activities and levels of GSH showed that SCHE did not reduce oxidative processes. In contrast, treatment with SCHE (1000 mg/kg b.w.) decreased liver MDA levels. Taken together, these findings suggested the chemopreventive effect attributed to SCHE in colon carcinogenesis, may be related to its capacity to inhibit DNA damage as well as an antioxidant action associated with its chemical constituents egonol and homoegonol.

Probing the chemoprevention potential of the antidepressant fluoxetine combined with epigallocatechin gallate or kaempferol in rats with induced early stage colon carcinogenesis.

The enhanced chemopreventive action against 1,2 Dimethylhydrazine (DMH)-induced preneoplastic lesion in rats could be achieved via simultaneous administration of the antidepressant fluoxetine (FLX) with two natural polyphenolic compounds viz., kaempferol (KMP) and/or epigallocatechin-gallate (EGCG). The obtained results revealed that single FLX pre-treatment possess a significant apoptotic effect by increasing the activity of serum and colon tissue caspase 3. It also attenuated the DMH driven increase in, colon tissue MDA, NO, PCNA and COX-2 expression as well as serum and colon tissue ß-catenin, with a decrease in the multiplicity of ACF and number of MPLs. The combination of FLX with either KMP or EGCG improved the antioxidant, anti-inflammatory and antiproliferating activities but with higher apoptotic activity in case of KMP. Eventually, histopathological assessment of colon tissues exposed that while sole pre-treatment can improve DMH-induced hyperplasia with only moderate inflammatory infiltration, tissues from the combined pre-treatment regimens groups exhibited almost a normal colonic architecture with slight submucosal edema. The study proved that single FLX administration prior to DMH exerts a chemopreventive effect and that the investigated combined pre-treatment regimens demonstrated more potent chemopreventive and antiproliferative actions.

Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.

BACKGROUND: Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC. AIM: To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis. METHODS: DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG. RESULTS: At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively. CONCLUSION: EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.

Techniques to Improve Photodynamic Therapy.

Photodynamic therapy [dye-light therapy] is an excellent technique for use in detection and treatment of cancerous tissues. While this therapy is effective, it is limited by the phototoxic reactions that can occur in the surrounding normal tissues. These damaging side effects are of particular importance when treating neurosensory organs, such as the human eye. We report here new treatment strategies to enhance photodynamic effectiveness while limiting side effects to normal tissues.

Reversible photochromic photocatalyst Bi2O3/TiO2/Al2O3 with enhanced visible photoactivity: application toward UDMH degradation in wastewater.

1,1-Dimethylhydrazine (UDMH) and its by-products were considered carcinogenic toxins and represent a serious health hazard to the population once present in water under natural conditions without treatment. The conventional degradation method suffers from incomplete removal of intermediate products (especially N-nitrosodimethylamine (NDMA)), the powdery catalysis being difficult to recover and results in high energy consumption. In this study, a series of Bi2O3/TiO2/Al2O3 (BTA) photocatalysts have been successfully synthesized by a simple dry mixing method with powder material followed by their immobilization. It was evaluated by the photocatalytic degradation of UDMH present in wastewater, which can be recovered by rapid filtration and utilizes only solar energy. The catalyst exhibited markedly enhanced photocatalytic activity for the degradation of UDMH wastewater compared with conventional TiO2/Al2O3 (TA) catalysts under UV, visible and solar irradiation. Besides, the intermediate NDMA was gradually completely degraded. The photocatalysts were extensively characterized using scanning electron microscopy, energy dispersive spectrometry, specific surface area (BET), X-ray diffraction, X-ray photoelectron spectroscopy, UV-visible diffuse reflectance spectroscopy and photo-electrochemical I-t curves evaluation. The results revealed that all the BTA composites exhibited high stability and stronger absorbance in visible light. In addition, the BTA exhibited a reversible photochromic property that can effectively expand the range of light absorption and enhance the photocatalytic activity. The reversible photochromic properties of BTA explained in the proposed mechanism model are expected to be useful for detecting and sensing UDMH or other organic contaminants.

Probiotic supplementation attenuates the aggressiveness of chemically induced colorectal tumor in rats.

To evaluate the effect of a probiotic on the aggressiveness of a chemically induced colorectal tumor in rats. Twenty-five male Fisher 344 rats, 250 g, provided with feed and water ad libitum, were randomly divided into 5 groups (5 rats/group): GControl, no treatment; GTumor, tumor induction; GTumor+5FU, tumor induction, 5-Fluorouracil applied; GTumor+Prob, induction of the tumor, supplemented with probiotic; GTumor+5-FU+Prob, tumor induction, 5-Fluorouracil applied, supplemented with probiotic. For tumor induction 20 mg/kg of 1,2-dimethylhydrazine was applied intraperitoneally over 4 weeks, followed by an interval of 15 days, and then repeated for a further 4 weeks. Five weeks after the final dose of the carcinogen, treatment was initiated with 5-Fluorouracil (15 mg/kg, intraperitoneally/week) and a commercial probiotic (1 × 109 CFU, daily/gavage). Data were analyzed by One Way Variance Analysis and means compared by Dunnett's test. GraphPad Prism statistical software was used. The histopathological analyzes were evaluated by the chi-square test. A 5% type-I error was considered statistically significant. Compared with the GTumor, the GTumor+Prob (p < 0.0373) and GTumor+5-FU+Prob (p < 0.0003) demonstrated an attenuated effect on the aggressiveness of the colorectal tumor, with a reduction in the count of Aberrant Crypt foci; and a lower percentage of malignant neoplastic lesions in the GTumor+Prob (40% low grade tubular adenoma, 40% carcinoma in situ, 20% low grade adenocarcinoma) and GTumor+5-FU+Prob (40% low grade tubular adenoma and 60% carcinoma in situ). Probiotic supplementation has the potential to decrease the formation of aberrant crypts and ameliorate tumor malignancy, enhancing the antitumor effect of 5-Fluorouracil chemotherapy in colic segments.

Co-administration of a probiotic strain Lactobacillus plantarum LS/07 CCM7766 with prebiotic inulin alleviates the intestinal inflammation in rats exposed to N,N-dimethylhydrazine.

The aim of this study was to determine the anti-inflammatory effects of preventive administration of a probiotic strain Lactobacillus plantarum LS/07 CCM7766 alone or in combination with prebiotic inulin or with flax-seed oil in the gut of rats, which developed chronic inflammation following administration of the pro-carcinogen N,N-dimethylhydrazine (DMH). After 28weeks administration of probiotic/prebiotic-containing diet, rats were killed and their colons were examined by immunohistological criteria, whereas cytokines were determined in the jejunal mucosa. Application of DMH triggered the production of pro-inflammatory cytokines IL-2, IL-6, IL-17, and TNF-α, expression of pro-inflammatory mediators NF-κB, COX-2 and iNOS and caused depletion of goblet cells. Supplementing the diet with L. plantarum and its combination with the prebiotic abolished DMH-induced inflammatory process in the jejunal mucosa by inhibiting the production of pro-inflammatory cytokines and by stimulation of anti-inflammatory IL-10 cytokine synthesis, whereas concentration of TGF-ß1 was not influenced significantly. Diet prevented a decrease in goblet cell numbers but numbers of mast cells were lowered only moderately. However, combined treatment of rats with L. plantarum and flax-seed oil had no significant effect on the parameters examined, except for decreased expression of NF-κB, in comparison with the negative control. Results indicate that the preventive administration of probiotic L. plantarum LS/07 CCM7766 alone or in combination with prebiotic inulin to rats with DMH-induced chronic inflammation can reduce inflammatory process in the jejunal and colon mucosa, probably indirectly, and involves down-regulation of synthesis of pro-inflammatory cytokines and suppression of NF-κB activity in mucosal cells.

Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment.

In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 µg 5-FU/g rat colon content vs 4.66 µg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.

Chemopreventive and metabolic effects of inulin on colon cancer development.

Prebiotics modulate microbial composition and ensure a healthy gastrointestinal tract environment that can prevent colon cancer development. These natural dietary compounds are therefore potential chemopreventive agents. Thirty Sprague-Dawley rats (4 months old) were experimentally treated with procarcinogen dimethylhydrazine to induce colon cancer development. The rats were randomly assigned to three groups: a control group (CG), a group treated with dimethylhydrazine (DMH), and a group given DMH and inulin, a prebiotic (DMH+PRE). The effects of inulin on the activities of bacterial glycolytic enzymes, short-chain fatty acids, coliform and lactobacilli counts, cytokine levels, and cyclooxygenase-2 (COX-2) and transcription nuclear factor kappa beta (NFκB) immunoreactivity were measured. Inulin significantly decreased coliform counts (p < 0.01), increased lactobacilli counts (p < 0.001), and decreased the activity of ß-glucuronidase (p < 0.01). Butyric and propionic concentrations were decreased in the DMH group. Inulin increased its concentration that had been reduced by DMH. Inulin decreased the numbers of COX-2- and NFκB-positive cells in the tunica mucosae and tela submucosae of the colon. The expression of IL-2, TNFα, and IL-10 was also diminished. This 28-week study showed that dietary intake of inulin prevents preneoplastic changes and inflammation that promote colon cancer development.

A Bayesian, generalized frailty model for comet assays.

This paper proposes a flexible modeling approach for so-called comet assay data regularly encountered in preclinical research. While such data consist of non-Gaussian outcomes in a multilevel hierarchical structure, traditional analyses typically completely or partly ignore this hierarchical nature by summarizing measurements within a cluster. Non-Gaussian outcomes are often modeled using exponential family models. This is true not only for binary and count data, but also for, example, time-to-event outcomes. Two important reasons for extending this family are for (1) the possible occurrence of overdispersion, meaning that the variability in the data may not be adequately described by the models, which often exhibit a prescribed mean-variance link, and (2) the accommodation of a hierarchical structure in the data, owing to clustering in the data. The first issue is dealt with through so-called overdispersion models. Clustering is often accommodated through the inclusion of random subject-specific effects. Though not always, one conventionally assumes such random effects to be normally distributed. In the case of time-to-event data, one encounters, for example, the gamma frailty model (Duchateau and Janssen, 2007 ). While both of these issues may occur simultaneously, models combining both are uncommon. Molenberghs et al. ( 2010 ) proposed a broad class of generalized linear models accommodating overdispersion and clustering through two separate sets of random effects. Here, we use this method to model data from a comet assay with a three-level hierarchical structure. Although a conjugate gamma random effect is used for the overdispersion random effect, both gamma and normal random effects are considered for the hierarchical random effect. Apart from model formulation, we place emphasis on Bayesian estimation. Our proposed method has an upper hand over the traditional analysis in that it (1) uses the appropriate distribution stipulated in the literature; (2) deals with the complete hierarchical nature; and (3) uses all information instead of summary measures. The fit of the model to the comet assay is compared against the background of more conventional model fits. Results indicate the toxicity of 1,2-dimethylhydrazine dihydrochloride at different dose levels (low, medium, and high).

Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.

BACKGROUND: Colon carcinogenesis is a multistep process and it emanates from a series of molecular and histopathological alterations. Glycyrrhizic acid (GA) is a natural and major pentacyclic triterpenoid glycoside of licorice roots extracts. It has several pharmacological and biological properties such as anti-inflammatory, anti-viral, and anti-cancer. In the present study, we investigated the chemopreventive potential of GA against 1,2-dimethyhydrazine (DMH)-induced precancerous lesions i.e., aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats. METHODS: Animals were divided into 5 groups. In group III, IV and V, GA was administered at the dose of 15 mg/kg b. wt. orally while in group II, III and IV, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b.wt once a week for first 5 weeks and animals were euthanized after 9 weeks. RESULTS: GA supplementation suppressed the development of precancerous lesions and it also reduced the infiltration of mast cells, suppressed the immunostaining of Ki-67, NF-kB-p65, COX-2, iNOS and VEGF while enhanced the immunostaining of p53, connexin-43, caspase-9 and cleaved caspase-3. GA treatment significantly attenuated the level of TNF-α and it also reduced the depletion of the mucous layer as well as attenuated the shifting of sialomucin to sulphomucin. CONCLUSION: Our findings suggest that GA has strong chemopreventive potential against DMH-induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of GA.

Chemopreventive and metabolic effects of inulin on colon cancer development

Prebiotics modulate microbial composition and ensure a healthy gastrointestinal tract environment that can prevent colon cancer development. These natural dietary compounds are therefore potential chemopreventive agents. Thirty Sprague-Dawley rats (4 months old) were experimentally treated with procarcinogen dimethylhydrazine to induce colon cancer development. The rats were randomly assigned to three groups: a control group (CG), a group treated with dimethylhydrazine (DMH), and a group given DMH and inulin, a prebiotic (DMH+PRE). The effects of inulin on the activities of bacterial glycolytic enzymes, short-chain fatty acids, coliform and lactobacilli counts, cytokine levels, and cyclooxygenase-2 (COX-2) and transcription nuclear factor kappa beta (NFkappaB) immunoreactivity were measured. Inulin significantly decreased coliform counts (p < 0.01), increased lactobacilli counts (p < 0.001), and decreased the activity of beta-glucuronidase (p < 0.01). Butyric and propionic concentrations were decreased in the DMH group. Inulin increased its concentration that had been reduced by DMH. Inulin decreased the numbers of COX-2- and NFkappaB-positive cells in the tunica mucosae and tela submucosae of the colon. The expression of IL-2, TNFalpha, and IL-10 was also diminished. This 28-week study showed that dietary intake of inulin prevents preneoplastic changes and inflammation that promote colon cancer development.

Dietary folate suppresses DMH-induced colon carcinogenesis in a rat model and affects DMH-induced expression of four DNA repair enzymes.

This study investigated the potential role of folate in the dimethylhydrazine (DMH) colon cancer model in male Wistar rats. For induction of colon cancer, group 1 rats were injected subcutaneously with 30 mg DMH/kg body weight weekly for 30 wk. Group 2 received DMH vehicle. Group 3 rats received DMH as in Group 1 but their diet was supplemented with 8 mg folate/kg diet. Group 4 was fed diet supplemented with 8 mg folate/kg diet. Upregulation of DNA damage repair genes Apurinic/apyrimidinic endonuclease 1, X-ray repair complementing defective repair in Chinese hamster cells 5, 8-oxoguanine-DNA glycosylase, and proliferating cell nuclear antigen, associated with a reduction of folic acid level was observed in colons of DMH group. Reductions of these gene upregulations and a significant increase of colonic folic acid level occurred in the DMH group supplemented with folic acid and this group also had significant inhibition of tumor incidence, normal survival rate and histologically nearly normal colonic architecture. It can be concluded that folate supplementation exerts a potent protective effect on rat colon carcinogenesis via significant modulation of DNA repair, providing a mechanism by which it plays a role in the etiology of human cancer.

Ras signaling pathway in the chemopreventive action of different ratios of fish oil and corn oil in experimentally induced colon carcinogenesis.

Dietary factors play a significant role in colon cancer. The essential polyunsaturated fatty acids (PUFAs), n-3 PUFAs, and n-6 PUFAs exert inverse effect on cancer. This study was designed to understand the mechanism of chemopreventive action of different ratios of fish oil (FO) and corn oil (CO) in colon carcinoma. Wistar rats were divided into 3 groups: Group 1 received purified diet whereas Groups 2 and 3 received modified diet with FO:CO (1:1) and FO:CO (2.5:1), respectively. The groups were further subdivided into controls receiving ethylenediamine-tetra acetic-acid and treated groups received dimethylhydrazine-dihydrochloride (DMH)/wk for 4 wk. Animals sacrificed 48 h after last injection constituted initiation phase and that sacrificed after 16 wk constituted post-initiation phase. Differential effect of different ratios of FO and CO was analyzed in isolated colonocytes. In both phases, DMH treatment showed an increase in pan Ras, Raf, MEK1/2, extracellular signal regulated kinase (Erk)1/2, and c-fos levels. Akt levels were increased in post-initiation phase only. Treatment with FO + CO (1:1) + DMH decreased pan Ras, MEK1/2 and Erk1/2 levels in post-initiation phase whereas Raf and c-fos were decreased in both phases. Treatment with FO + CO (2.5:1) + DMH decreased Ras, Raf, MEK1/2, Erk1/2, and c-fos levels in both phases. Akt was decreased in post-initiation phase only. The chemo-preventive action of FO and CO may be mediated by time- and dose-dependent effect.

Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

β-ionone (βI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight), GO (25 mg/100 g body weight), βI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the βI (91 ± 11 and 14 ± 3) and βI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry) were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcrvpdate=20110329inogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

[Results of study concerning possible influence of rocket space activities on public health].

Using special medical examination results and specified criteria of objective evaluation, the authors summarized results of studies concerning health state of population dwelling in area possibly influenced by rocket space activities factors.

Efficacy of geraniol but not of ß-ionone or their combination for the chemoprevention of rat colon carcinogenesis.

ß-ionone (ßI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of ßI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with ßI (16 mg/100 g body weight), GO (25 mg/100 g body weight), ßI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the ßI (91 ± 11 and 14 ± 3) and ßI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of ßI and GO (gas chromatography/mass spectrometry) were higher in the ßI and GO groups, respectively, compared to the control and ßI+GO groups. Therefore, GO, but not ßI, represents a potential chemopreventive agent in colon carcinogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.