Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Azoxymethane”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed2001

Sequential analysis of morphological and biological properties of beta-catenin-accumulated crypts, provable premalignant lesions independent of aberrant crypt foci in rat colon carcinogenesis.

Our previous study (Cancer Res., 60: 3323-3327, 2000) showed that frequent beta-catenin gene mutations are present in beta-catenin-accumulated crypts, which occur early in rodent colonic carcinogenesis, with a lack of the appearance of aberrant crypt foci (ACF). To clarify the nature of such lesions, we performed a sequential analysis of the morphological and biological properties of beta-catenin-accumulated crypts. Azoxymethane was administered s.c. to male F344 rats (15 mg/kg body weight) once a week for 3 weeks, and the animals were sacrificed at 5, 10, and 20 weeks after the carcinogen treatment. Both the number of crypts/lesion and the diameter of beta-catenin-accumulated crypts were significantly increased with time courses of 5, 10, and 20 weeks from carcinogen exposure (P < 0.01). Likewise, the histological abnormality in those crypts, assessed by semiquantitative analyses, was also increased with time (P < 0.01). Conversely, ACF did not show any increase in histological abnormality during the time course and maintained a monotonous histology throughout the experiment. The histological abnormality score for beta-catenin-accumulated crypts was significantly higher than for ACF at every time point (P < 0.001). The number of AgNOR/nucleus in beta-catenin-accumulated crypts was significantly higher than in ACF (P < 0.001). Beta-catenin-accumulated crypts were accompanied frequently by Paneth cells and had decreased hexosaminidase activity. Such data, together with the results in our previous report, strongly suggest that beta-catenin-accumulated crypts, which are independent of ACF, are truly premalignant lesions for colon cancer.

Animals↗
PubMed2001

Mechanisms of cancer chemoprevention by curcumin.

Curcumin is a major component of the Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animals as indicated by its ability to block colon tumor initiation by azoxymethane and skin tumor promotion induced by phorbol ester TPA. Recently, curcumin has been considered by oncologists as a potential third generation cancer chemopreventive agent, and clinical trials using it have been carried out in several laboratories. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes, such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase. Curcumin is also a potent inhibitor of protein kinase C, EGF-receptor tyrosine kinase and IkappaB kinase. In addition, curcumin inhibits the activation of NFkappaB and the expression of c-jun, c-fos, c-myc and iNOS. It is proposed that curcumin may suppress tumor promotion by blocking signal transduction pathways in the target cells. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin, and these compounds were subsequently convened into monoglucuronide conjugates. The experimental results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are major metabolites of curcumin in mice.

Animals↗
PubMed2002

COX-2 and prostanoid receptors: good targets for chemoprevention.

Accumulating evidence indicates that COX-2 inhibitors are involved in colon and breast cancer development. Our previous studies indicated that nimesulide and celecoxib, selective COX-2 inhibitors, show inhibitory effects of intestinal carcinogenesis in azoxymethane-treated rats and mice and in Min mice models. We recently found that nimesulide suppressed PhIP-induced breast cancer in female SD rats in which COX-2 protein was overexpressed. These results led us to investigate the effects of prostaglandin E2 (PGE2) in the target tissues. PGE2 showed its biological activity through binding to its membrane receptors, EP(1 to approximately 4). We also investigated the effects of EP receptors on colon carcinogenesis. We used receptor knockout mice and selective receptor antagonists. Our results indicated that the EP1 receptor plays a pivotal role in colon carcinogenesis. Selective EP1 receptor antagonists may be a new class of chemopreventive agents against colon cancer.

Animals↗
PubMed2002

Myristoyl-CoA:protein N-myristoyltransferase: a novel molecular approach for cancer therapy (Review).

Colorectal cancer is the second leading cause of malignant death, and better preventive strategies are needed. The treatment of colonic cancer remains difficult because of the lack of effective chemotherapeutic agents; therefore it is important to continue to search for cellular functions that can be disrupted by chemotherapeutic drugs resulting in the inhibition of the development and progression of cancer. The current knowledge of the modification of proteins by myristoylation involving myristoyl-CoA:protein N-myristoyltransferase (NMT) is in its infancy. This process is involved in the pathogenesis of cancer. We have reported for the first time in rats treated with azoxymethane that NMT activity was higher in colonic epithelial neoplasms than in normal colonic tissue and that an increase in NMT activity appeared at an early stage in colonic carcinogenesis. Increased NMT activity was also confirmed in human colonic tumors compared to normal tissue. Furthermore, colorectal tumors displayed increased immunohistochemical staining for NMT compared to normal mucosa in the cytoplasm. In addition, gallbladder carcinoma showed moderate to strong cytoplasmic positivity for NMT with increased intensity in the invasive component whereas the normal gallbladder mucosa showed weak to negative cytoplasmic staining for this enzyme. It is conceivable therefore that NMT can be used as a potential marker for the early detection of cancer. Of particular note is the very recent discovery of cytotoxic compounds in the laboratories of the authors which inhibit NMT and may offer a novel approach for the evolution of candidate antineoplastic agents which display greater potencies towards neoplasms than the corresponding normal tissues.

Acyltransferases↗
PubMed2000

Milk Components as Cancer Chemopreventive Agents.

Since milk and dairy products constitute very important ingredients of the western style diet, a large number of epidemiological studies have been conducted to determine effects of their consumption on neoplastic development. However, reflecting the variety of included components, the data are to some extent equivocal. It has been proposed that whereas fats in general might promote tumour development, individual milk fats like conjugated linoleic acid and glycosh\ingolipids could exert inhibitory effects. There is also considerable evidence that calcium in milk products protects against colon cancer, while promoting in the prostate through suppression of circulating levels of 1,25 dihydroxyvitamin D. Whey protein may also be beneficial, as shown by both animal and human studies, and experimental data have demonstrated that the major component bovine lactoferrin (bLF), inhibits colon carcinogenesis in the post-initiation stage in male F344 rats treated with azoxymethane (AOM) without any overt toxicity. Results in other animal models have provided further indications that bovine lactoferrin might find application as a natural ingredient of milk with potential for chemoprevention of colon and other cancers.

Journal Article↗
PubMed2000

Promotion of Liver Lesion Development in the Syrian Hamster by Dietary Fat Following Multi-organ Initiation is Inhibited by DHEA-S Administration.

The influence of dietary supplementation with dehydroepiandrosterone-sulphate (DHEA-S) at 0.6% was investigated in male Syrian golden hamsters initiated by treatments with azoxymethane(AOM), and dihydroxy-di-n-propyl nitrosamine (DHPN), timed after transfer from a choline-deficient to a normal diet. These carcinogens respectively target the colon, and the respiratory tract, the liver and pancreas. A total of 75 animals were divided into 6 groups, 1-3 (20 animals each) receiving the initiation protocol of during the first 8 weeks, and 4-6 (5 animals each) given the vehicles alone. The hamsters in groups 2,3 and 5,6 then received a high fat diet (20% corn oil) while DHEA-S was given in addition for 20 weeks to groups 3 and 6. Groups 1 and 4 served as controls on the basal diet. Assessment of development of preneoplastic and neoplastic lesions, after sacrifice at week 28, revealed increase in hepatocellular liver nodules and the index of BrdU incorporation in the hepatocellular cells of the liver in the initiated animals given the high fat diet. This was significantly reduced by the DHEA-S supplementation. Non-significant tendencies for high fat enhancement and hormone protection were also observed for lung and colon tumors.

Journal Article↗
PubMed2003

Induction of NAD(P)H quinone: oxidoreductase1 inhibits carcinogen-induced aberrant crypt foci in colons of Sprague-Dawley rats.

Phase II detoxifying enzymes like NAD(P)H (quinone acceptor)oxidoreductase1 (NQO1), glutathione S-transferases (GST), and UDP-glucuronyltransferases (UGT) may play an important role in preventing carcinogen-induced cancers. Inducers of these enzymes have been shown to inhibit carcinogen-induced colon tumors in rat and mouse models. However, it has not been clearly demonstrated that NQO1 contributes to this effect. We examined the effect of NQO1 inducers on colon carcinogenesis using an aberrant crypt foci (ACF) rat model. Sprague-Dawley rats were fed control diet or diet containing 400 ppm dimethyl fumarate or 200 ppm oltipraz for 7 days, and Phase II enzymes in rat colon and liver were measured. Dimethyl fumarate significantly increased NQO1 and GST activities in colon and liver but did not increase UGT activities in these tissues. In contrast, oltipraz significantly increased NQO1 activities in colon and liver and produced a small increase in GST activity in the liver but did not increase GST activity in the colon or UGT activities in the liver or colon. Sprague Dawley rats were fed control diet or diet containing 200 ppm oltipraz and then treated with the carcinogens azoxymethane or methyl nitrosourea. Both carcinogens produced ACF in all of the rat colons, but rats fed oltipraz diet had significantly fewer ACF than those fed control diet. This protective effect was reversed in rats treated with the NQO1 inhibitor, dicoumarol. However, treatment with oltipraz did not alter the distribution of crypt multiplicities in the ACF. These studies demonstrated that induction of NQO1 plays a significant role in inhibiting initiation of carcinogen-induced ACF in Sprague-Dawley rats. This provides the first direct evidence that NQO1 may play a role in preventing colon cancer. The study also found that oltipraz added to the diet of Sprague-Dawley rats selectively increased NQO1 activity in colon mucosa with no increase in GST and UGT activities in these tissues. Thus, this model will be useful for further investigating the role of NQO1 in prevention of colon cancer.

Animals↗
PubMed1992

Selenium in the treatment of heavy metal poisoning and chemical carcinogenesis.

Selenium (Se) has been shown to counteract the toxicity of heavy metals such as cadmium, inorganic mercury, methylmercury, thallium and to a limited extent silver. Although not as effective as Se, vitamin E significantly alters methylmercury toxicity and is more effective than Se against silver toxicity. Vitamin E is very effective against lead toxicity but Se has little effect. The presumed protective effect of Se against cadmium and mercury toxicity is through the diversion in their binding from low molecular weight proteins to higher molecular weight ones. Se appears effective in counteracting the chemical carcinogens (3-methyl-4-dimethyl-aminoazobenzene, 2-acetylaminofluorene, diethylnitrosamine, aflatoxin, 7,12-dimethylben (a) anthracene, benzopyrene and 3-methylcholanthrene) used to induce skin, liver and mammary tumors, but much less effective against those (dimethylhydrazine, azoxymethane, methylazoxymethanol, bis (2-oxopropyl) nitrosamine, benzopyrene, 1 methyl-1-nitrosourea and n-methyl-n-nitro-nitrosoguanidine) used to produce tumors in the colon, lungs, trachea and pancreas in laboratory animals. In contrast, Se many even increase pancreatic carcinomas in animals treated with bis (2-oxopropyl) nitrosamine. The health implications in humans of Se and heavy metal toxicities and in cancer are discussed.

Animals↗
PubMed1992

Nonresponsiveness of the rat liver to alkylating carcinogens given by gavage.

Carcinogenic alkylating agents administered orally are metabolized in the liver and alkylate DNA in liver cells of rats and hamsters. They frequently, but not always, induce liver tumors, in addition to tumors of other organs. Directly acting alkylating agents, such as alkylnitrosoureas and alkylnitrosocarbamates, rarely induce liver tumors, although they alkylate DNA in liver cells. The methylating agents nitrosodimethylamine and azoxymethane induce high incidences of liver tumors in rats when given in drinking water, but few or no liver tumors when given by gavage, although the total dose and the weekly dose were the same in either regimen. In contrast, methylnitrosoethylamine and nitrosodiethylamine give rise to liver tumors in rats in high incidences whether given by gavage or in drinking water. Sharp differences are also observed with other nitrosamines, such as those containing a propyl group with an oxygen substituent in the 2-position. These discrepancies indicate that, in addition to alkylation of DNA, pharmacokinetics of dosing and distribution and other reactions of the carcinogen are the dominant factors in determining the development of tumors in the liver.

Administration, Oral↗
PubMed1992

Chemoprevention of colon carcinogenesis by the synthetic organoselenium compound 1,4-phenylenebis(methylene)selenocyanate.

The chemopreventive effect of 40% and 80% maximum tolerated dose (MTD) levels of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) administered in the diet during the initiation phase (2 weeks before, during, and up to 3 days after carcinogen administration) and the post-initiation phase (3 days after carcinogen treatment until termination) of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD of p-XSC was determined in male F344 rats and found to be 50 ppm. Beginning at 5 weeks of age, all animals were divided into various experimental groups (42 rats/group) and fed the high-fat semipurified diet or diets containing 20 (40% MTD) and 40 (80% MTD) ppm p-XSC. At 7 weeks of age, all animals (30 rats/group) except the vehicle-treated groups (12 rats/group) were administered s.c. injections of AOM (15 mg/kg body weight/week for 2 weeks). Three days after the second injection of AOM or vehicle (normal saline), groups of animals fed the p-XSC diets and control diet were transferred, respectively, to control diet and p-XSC diets and continued on these diets until the termination of the study. All animals were necropsied during the 36th week after AOM treatment. Colonic mucosal prostaglandin E2 and selenium-dependent glutathione peroxidase were measured in animals fed the control and p-XSC diets at the termination of the study. The results indicate that 40 ppm p-XSC administered during the initiation phase significantly inhibited the colon tumor incidence (percentage of animals with tumors). Dietary p-XSC administered at 20 and 40 ppm levels during the initiation phase significantly inhibited colon tumor multiplicity (tumors/animal and tumors/tumor-bearing animal). Colon tumor incidence and multiplicity were significantly reduced in groups fed 20 and 40 ppm p-XSC diets at the postinitiation phase of carcinogenesis. Colonic mucosal selenium-dependent glutathione peroxidase activity was increased, and prostaglandin E2 was reduced in animals fed the p-XSC diet compared to animals fed the control diet. Whereas the precise mechanisms of p-XSC-induced inhibition of colon carcinogenesis remain to be elucidated, it is likely that the effect during the initiation and postinitiation phases may be due to alteration in carcinogen metabolism and to modulation of prostaglandin synthesis and selenium-dependent glutathione peroxidase activity.

Adenocarcinoma↗
PubMed2004

Overexpression of caveolin-1 in experimental colon adenocarcinomas and human colon cancer cell lines.

Caveolin-1, -2, and -3 are the principal proteins of caveolae, the vesicular invaginations of the plasma membrane. Recent studies suggest that caveolins play an important role in cellular signaling and, possibly, in tumorigenesis. We examined the expression of the three caveolins in azoxymethane-induced rat colon adenocarcinoma and normal-appearing colonic mucosa, and also in human colon cancer cells with inherently different proliferation rates. Expression of caveolins was assessed in experimental rat colon adenocarcinoma and normal-appearing colonic tissues by RT-PCR, immunoblot and immunohistochemistry. Expression of caveolin-1, -2, and -3 at protein and mRNA levels in human colon cancer cell lines Caco-2, HT-29 and HCT-116 was assessed by immunoblot and RT-PCR, respectively. While caveolin-1 was overexpressed in all experimental adenocarcinoma tissues by comparison to normal-appearing colonic mucosa at both the mRNA and protein level, caveolin-2 was expressed equally only at the mRNA level in both tissues. Immunohistochemical analysis of experimental rat colon tissues also revealed a similar pattern with caveolin-1 being overexpressed in adenocarcinomas as compared to normal-appearing colonic mucosa. Caveolin-1 protein expression was observed in HT-29 and HCT-116 cell lines but not in the Caco-2 cell line or the macrophage Raw 264.7 cell line. Caveolin-1 mRNA expression was evident in all colon carcinoma cell lines tested; however, caveolin-2 mRNA was found only in HT-29 and HCT-116. Caveolin-1 protein and mRNA transcript levels in human colon cancer cell lines were observed to be concordant with the growth rate of the cells, and followed the pattern of HCT-116 > HT-29 > Caco-2. Taken together, our results indicate that caveolin-1 is overexpressed in experimental colon adenocarcinoma by comparison to adjacent normal mucosa, and its expression in human colon cancer cells is directly associated with the growth rate.

Adenocarcinoma↗
PubMedDate not supplied

Indian food ingredients and cancer prevention - an experimental evaluation of anticarcinogenic effects of garlic in rat colon.

The major food items of Indian cuisine include rice, wheat, diary products, and abundant fruits and vegetables. Beside these, there are several kinds of herbs and spices as important ingredients, containing many phytochemicals with medicinal properties, adding taste to Indian cuisine. An impressive body of data exists in support of the concept that Indian food ingredients can be used in preventive strategies aimed at reducing the incidence and mortality of different types of cancers because of their antioxidative, antimutagenic and anticarcinogenic properties. Vital ingredients used in Indian cooking include turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic Garlic is an indispensable ingredient of Indian food and this report concerns the chemopreventive efficacy of garlic in an azoxymethane induced rodent colon carcinogenesis model. The effect of garlic was evaluated in terms of aberrant crypt foci, putative preneoplastic lesions in the colon. In addition, cell proliferation and levels of apoptosis were determined and the expression of cyclooxygenase-2 protein was analyzed. Following treatment, significant inhibition of cell proliferation and induction of apoptosis, as well as suppression of cyclooxygenase-2 activity were observed, associated with significant reduction in the incidence of aberrant crypt foci. The study points to combined protective effects of garlic components on colon carcinogenesis.

Analysis of Variance↗
PubMedDate not supplied

Combinatorial chemoprevention: efficacy of lovostatin and exisulind on the formation and progression of aberrant crypt foci.

BACKGROUND: There are several advantages to combinatorial chemoprevention strategies over monotherapeutic approaches. Both the HMG-CoA reductase inhibitor (HRI) lovastatin (LOV) and the selective apoptotic antineoplastic drug (SAAND) exisulind (EXS) have shown remarkable chemopreventive effects in previous studies, in cell lines and limited studies in rodents. Here, experiments were designed to assess the potential use of these two compounds in combinatorial chemoprevention therapy, using two bio-assays in which inhibition of the carcinogen-induced preneoplastic lesions, aberrant crypt foci (ACF), was used to quantitate efficacy. MATERIALS AND METHODS: ACF were induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential weekly i.p. injections at a dose of 15 mg/kg. F344 rats were fed seven experimental diets containing LOV @ 50 parts per million (ppm), EXS @ 100, 250 and 1000 ppm and combination diets containing EXS at 100, 250 and 1000 ppm, each combined with LOV @ 50 ppm. Quantification of ACF number and type (singlet, doublet, triplet and four or more) was performed on whole mounts of rat colons stained with 1.0% methylene blue. RESULTS: During the initiation protocol, administration of LOV @ 50 ppm alone and the combination of LOV @ 50 ppm with EXS @ 1000 ppm significantly decreased the mean number of ACF when compared to the positive control by 49% and 47%, respectively; however EXS @ 250 ppm displayed tumor promoting effects by significantly increasing the mean number of ACF by 64%. The post-initiation protocol administration of EXS @ 100, 250 and 1000 ppm and the combinations of LOV @ 50 ppm with EXS @ 100 and 250 ppm significantly increased the mean number of ACF when compared to the positive control by 44%, 48%, 55%, 49% and 40%, respectively. CONCLUSION: LOV shows greater promise than EXS in fulfilling the role as a supplemental chemopreventive agent in combinatorial chemopreventive strategies for cancers such as colon cancer. EXS did not augment this activity, failing to enhance chemopreventive therapy in this animal model.

Animals↗
PubMed1992

Dietary and erythrocyte fatty acids in experimental colorectal carcinogenesis.

The influence of dietary fat on the erythrocyte stearic:oleic acid ratio was investigated in an experimental model of colorectal cancer. One hundred male Wistar rats were divided into four separate dietary groups: A (5% saturated fat), B (20% saturated fat), C (5% n-6 unsaturated fat) or D (20% n-6 unsaturated fat). Colorectal tumours were induced by intraperitoneal injection of azoxymethane (n = 60) and control animals received saline (n = 40). Animals were killed after 26 weeks and erythrocyte fatty acid profiles were determined by gas liquid chromatography. Although there were no differences in the incidence of adenoma formation in the four dietary groups, there was a significantly lower incidence of carcinomas in rats fed a 5% or 20% unsaturated fat diet when compared with either a 5% (P less than 0.05) or a 20% saturated fat diet (P less than 0.01). Multivariate analysis of fatty acid profiles demonstrated that both the type and quantity of dietary fat had a highly significant influence on the fatty acid profile of erythrocytes. The stearic:oleic acid ratio varied considerably between the four dietary groups but was only significantly lower in tumour bearing animals compared with controls in group B (20% saturated fat diet).

Animals↗
PubMedDate not supplied

Ketoprofen-inhibited N-acetyltransferase activity and gene expression in human colon tumor cells.

The activation of ketoprofen, which inhibits the outgrowth of azoxymethane-induced aberrant crypt foci in the rat colon, on the inhibition of arylamine N-acetyltransferase (NAT) activity (N-acetylation of substrates), gene expression (mRNA NAT) and 2-aminofluorene (AF)-DNA adduct formation was studied in a human colon tumor (adenocarcinoma) cell line (colo 205). Cellular cytosols (9000 xg supernatant) and intact colon tumor cells were used. The NAT activity in colo 205 cells was inhibited by ketoprofen in a dose- and time -dependent manner in both examined systems. The data also indicated that ketoprofen decreased the apparent value of V(max) of NAT enzymes, being a competitive inhibitor of NAT enzymes. The AF-DNA adduct formation in colo 205 cells was also decreased by ketoprofen. Based on the results from PCR, it was shown that ketoprofen affected mRNA NAT expression in human colon colo 205 cells. The cells were stained with anti-NAT antibody, then analyzed by flow cytometry. The results showed that ketoprofen decreased the percentage of cells stained by anti-NAT. This report is the first to demonstrate that ketoprofen inhibits human colon tumor cell NAT activity, gene expression and DNA adduct formation.

2-Acetylaminofluorene↗
PubMed2006

Fulminant liver failure triggered by therapeutic antibody treatment in a mouse model.

Monoclonal antibodies are finding ever increasing therapeutic applications. However, lethal liver damage has been reported following monoclonal antibody (mAb) treatment in combination with subtoxic doses of cytotoxic drugs. In this study, mice were intravenously injected with 200 microg/mouse of anti-CD8 (anti-Lyt-2.2), anti-CD4 (GK1.5) or anti-B220 (RA3-6B2) mAb. Subsequently, mice were administered 15 mg azoxymethane (AOM) per kg body weight by subcutaneous injection. Unexpectedly, all mice pretreated with mAb died within 72 h of a single injection of AOM. The injection of mAb-coated spleen cells accelerated the induction and the severity of liver disease. We found that mAb treatment activates Kupffer cells to produce inflammatory cytokines such as TNF-alpha and IL-12, and induces the expression of FasL on Kupffer and NKT cells. The concomitant upregulation of Fas on hepatocytes increases the susceptibility of the liver to apoptotic signals, and subsequent treatment with AOM causing mitochondrial injury synergistically induces lethal liver damage. Consistently, the lethal liver damage was abrogated in mice which were deficient for Kupffer cells, NKT cells or Fas-antigen. In conclusion, we have demonstrated a potential risk of lethal fulminant liver damage in the concomitant use of therapeutic antibodies and cytotoxic drugs. A possible side effect of antibody therapy is mediated through activation of the immune system, the very mechanism of action on which this treatment depends. In this context, the risk of combining therapeutic antibodies with other agents, particularly cytotoxic drugs, requires careful consideration.

Animals↗
PubMedDate not supplied

Preventive effect of fluvastatin on ulcerative colitis-associated carcinogenesis in mice.

An increased incidence of colorectal carcinoma is known to occur in patients with ulcerative colitis (UC), which displays a cycle of recurrence-remission in the colorectal mucosa. Fluvastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, is a hypocholesterolemic agent effective in animals and humans. Repeated administration of 3% dextran sulfate sodium subsequent to a single intraperitoneal injection of azoxymethane induces chronic UC resulting in an increased incidence of high-grade dysplasia and submucosal-invasive adenocarcinomas in the mouse colorectum. The effects of fluvastatin as an antioxidant on colorectal carcinogenesis in mice with UC were investigated. Treatment with fluvastatin in mice with UC abolished the anemia caused by colorectal carcinogenesis, and markedly lowered plasma lipid levels resulting in a reduction of colitis and carcinogenesis, shown by inhibition of the decrease in colorectal length, the increased number of foci of gland loss with inflammatory cell infiltration indicating the severity of UC and incidence of colorectal dysplasia, respectively, with a reduction in anti-8-hydroxy-2'-deoxyguanosine (8-OHdG) antibody (a biological marker of in vivo oxidative DNA damage)-positive cells of the colorectal mucosa and the activity of the DNA-synthesizing enzyme thymidine kinase in colorectal tissues.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1989

Carcinogenesis by nitrosamines and azoxyalkanes by different routes of administration to rats.

The effects of administering similar doses of some simple alkylating agents to rats by different regimens have been compared. Two of the compounds were methylating agents, nitrosodimethylamine and azoxymethane; two were ethylating agents, nitrosodiethylamine and azoxyethane; and nitrosomethylethylamine was both a methylating and an ethylating agent. The treatments gave rise to tumors in almost all treated rats. The results indicate the importance of pharmacokinetics in determining which organs are the targets of the alkylating carcinogens.

Administration, Intravesical↗