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At least 19 recordsLinked to original sources

PubMed2005

Determination of hydrazine, monomethylhydrazine, 1,1-dimethylhydrazine, and 1,2-dimethylhydrazine by nonaqueous capillary electrophoresis with amperometric detection.

The present study is concerned with the application of nonaqueous capillary electrophoresis (NACE) with electrochemical detection (ED) to the separation and quantitative determination of hydrazine (Hy) and its methyl derivatives. The best performance of NACE-ED was found when using 4 mM sodium acetate/10 mM acetic acid/methanol: acetonitrile = 1:2 as the running buffer, with a bare platinum working electrode set at +1.0 V in an end-column amperometric detection cell. The choice and ratio of suitable solvents for the separation and injection media played an essential role for the performance characteristics of the method. The limits of detection for Hy, methylhydrazine, symmetrical dimethylhydrazine, and unsymmetrical dimethylhydrazine were 5, 2, 12, and 1 ng/mL, respectively. This is between one and two orders of magnitude lower than that achieved by previously reported CE-ED methods in aqueous buffer systems in conjunction with various types of chemically modified electrodes. The practical utility of the new NACE-ED methodology is demonstrated in terms of the determination of traces of Hys in spiked environmental samples containing a wide range of explosives and related compounds.

1,2-Dimethylhydrazine↗

PubMed1985

A comparative study of dimethylhydrazine regioisomers and the methylazoxymethanol metabolite of 1,1- and 1,2-dimethylhydrazine in relation to transformation in human fibroblasts.

Comparative analysis of the cytotoxicity, transformation efficiency, induction of alkali labile sites (ALS) and DNA methylation in human foreskin fibroblasts was carried out with two dimethylhydrazine (DMH) regioisomers (1,1-DMH and 1,2-DMH) and the acetate (A) derivative of the metabolite methylazoxymethanol (MAM) of 1,2-DMH. Effective ED50 cytotoxic doses for MAMA, 1,1-DMH and 1,2-DMH were 0.056, 6.83 and 6.30 mM, respectively. MAMA and 1,1-DMH were more effective transformers than 1,2-DMH. However, methylation of purines accounted for less than 1% of the total radiolabel associated with DNA for all 3 agents. 1,2-DMH, 1,1-DMH and MAMA induced O6MeGua/N7MeGua ratio of 0.04, 0.32 and 0.18, respectively. Only MAMA induced measurable alkali labile lesions at transforming doses. These results suggest that other mechanisms may play a role in the initiation of transformation events by hydrazine analogues.

1,2-Dimethylhydrazine↗

PubMed1976

Cell proliferation in the descending colon of dimethylhydrazine treated rats and in dimethylhydrazine induced adenocarcinomata.

A stathmokinetic technique which has estimable precision has been used to estimate mitotic rates in the crypts of Lieberkühn in the descending colon of normal, and of dimethylhydrazine (DMH)-treated rats, as well as in DMH-induced adenocarcinomata. Estimates of the mean number of proliferating and of non-proliferating cells per crypt of Lieberkühn were also made in normal and in DMH-treated rats. In normal rats, epithelial cell proliferation was found to be relatively slow in the basal one-fifth of the crypts of Lieberkühn and to be most rapid in the second one-fifth of the crypt. In DMH-treated rats the number of cells around the circumference of transversely sectioned crypts was significantly increased, as was the number of proliferating cells present in longitudinally sectioned crypts. The region of relatively slow cell proliferation in the base of the crypts was expanded to occupy the lower two-fifths of the crypt in DMH-treated rats whilst the region of most rapid cell proliferation was displaced upwards to occupy the third one-fifth of the crypt. In DMH-induced adenocarcinomata cell proliferation occurred at a rate similar to that in the relatively quiescent zone at the bases of the colinic crypts in normal animals. However, tumour cell proliferation was substantially slower than that in the second one-fifth of the crypt in normal animals.

Adenocarcinoma↗

PubMed1982

Pathogenesis of 1,2-dimethylhydrazine-induced carcinomas in rat intestine. II. Histochemical and ultrastructural characteristics of glycoproteins of 1,2-dimethylhydrazine-induced carcinoma cells.

Two hundred twenty seven lesions of DMH-induced intestinal carcinomas of 68 male Wistar rats were investigated by means of histochemical and electron microscopic properties to study their histogenesis and mucinogenesis. Among the epithelial glycoproteins, surface glycoprotein on the microvilli with glycocalyces was distinguishable from mucin in the cytoplasm based on histochemical staining and ultrastructural findings. From the phenotypic characteristics of glycoproteins, it was suggested that DMH-induced carcinomas could be classified into mucin producing carcinomas composed mainly of cells containing intracellular mucins and non-mucin producing ones. The mucin producing carcinomas consisted of poorly differentiated adenocarcinoma, signet ring cell carcinoma, and mucinous carcinoma presumably resulting from various degrees of differentiation into goblet cells. Their staining attitude varied and cells with neutral mucin, sialomucin and sulphated mucin were observed in the signet ring cell carcinoma. In addition, abnormal synthesis of glycoproteins was observed with ConA-paradox staining and PATS/PB/KOH/PAS. These histochemical properties suggested irregulatory synthesis of glycoproteins in carcinomas. In non-mucin producing carcinomas, glycoproteins were found mainly on the apical surface and contained sialomucin. A deviated differentiation into an absorptive cell could form an intracytoplasmic cyst filled with an aggregation of glycocalyces, so becoming another type of signet ring cell.

1,2-Dimethylhydrazine↗

PubMed1990

Effect of germanium on 1,2-dimethylhydrazine-induced intestinal cancer in rats.

Through recent research, the trace element, germanium, was found to have an anticancer effect. The purpose of this research was to determine the effect of germanium on 1,2-dimethylhydrazine-induced intestinal cancer in rats. Ninety-six 8-week-old Sprague-Dawley male rats were divided into 4 groups, with 24 rats in each group. All received dimethylhydrazine, 20 mg/kg body weight, subcutaneously, once a week for 20 weeks. Except for one control group, the other three groups were subdivided into six groups and administered three different kinds of germanium (inorganic germanium, organic germanium, and natural organic germanium) one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment, respectively. Twenty-four weeks after carcinogen exposure, all surviving animals were sacrificed and examined for intestinal tumors. The number and location of the tumors were recorded and the pathology examined. The incidence of intestinal cancer in the control group (dimethylhydrazine only) was 91 percent; in groups provided with inorganic germanium one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only, it was 91 and 78 percent; in groups provided with organic germanium one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only, it was 64 and 64 percent; in groups provided with natural organic germanium one month before and during dimethylhydrazine treatment and during dimethylhydrazine treatment only, it was 50 and 45 percent. From these results, the authors conclude that natural organic germanium has the best prevention effect for intestinal cancer in this animal model (P less than 0.01), followed by organic germanium (P less than 0.05). Inorganic germanium has no effect. However, there is no difference in the cancer prevention effect of germanium provided one month before and during dimethylhydrazine treatment, and during dimethylhydrazine treatment only.

1,2-Dimethylhydrazine↗

PubMed1997

Effects of epidermal growth factor and dimethylhydrazine on crypt size, cell proliferation, and crypt fission in the rat colon. Cell proliferation and crypt fission are controlled independently.

Crypt fission is now established as an important mechanism of intestinal growth and regeneration. It has been proposed that increased crypt size is the stimulus for crypt fission, because crypts preparing for fission are generally larger. Consequently, we investigated the effects of epidermal growth factor (EGF) and dimethylhydrazine, which are both known to stimulate crypt cell proliferation, on crypt fission in the rat intestine. We also examined whether the effects of EGF on both proliferation and crypt fission are modified by the pretreatment with dimethylhydrazine for 16 weeks, dimethylhydrazine was then discontinued for 8 weeks, followed by intravenous infusion of EGF for 1 week. There were four groups: vehicle alone, EGF alone, dimethylhydrazine alone, and dimethylhydrazine followed by EGF infusion. The rats were killed at 25 weeks and rates of intestinal crypt cell production, crypt size, and crypt fission were determined. Intravenously infused EGF significantly increased crypt cell production rate, but the magnitude of the effect decreased from the proximal to the distal colon. EGF caused an increase in crypt area, possibly reflecting an increase in crypt size. Importantly dimethylhydrazine had no significant effect on crypt cell production rate nor on crypt area in the distal colon, but it did cause an increase in crypt area in the mid-colon. The crypt fission index was significantly decreased by EGF and increased by dimethylhydrazine. There was no qualitative interaction between EGF and dimethylhydrazine. These results demonstrate the marked proliferative effect of intravenously infused EGF in the colon of orally fed rats, with significant site effects (P = 0.0007); the effect was greatest in the proximal colon and disappeared in the distal colon. The observation that EGF reduced crypt fission indicates that increased cell proliferation, per se, is not a stimulus for crypt fission. This is further supported by the observation that dimethylhydrazine increases crypt fission in crypts of normal size in the distal colon without significantly increasing cell proliferation. These results suggest that increasing crypt cellularity by proliferation is not sufficient to induce crypt fission, and factors other than increased crypt size by proliferation can control crypt fission. It is also probable that cell proliferation and crypt fission are independently regulated. Crypt fission appears to play a considerable role in the intestinal response to carcinogens.

Animals↗

PubMed2006

Effect of ginger on bacterial enzymes in 1,2-dimethylhydrazine induced experimental colon carcinogenesis.

Colon cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer death in the United States. Ginger, a natural spice having both antioxidant and antimutagenic property, is known to inhibit chemical carcinogenesis. This study was designed to investigate the chemopreventive efficacy of ginger on the activity of bacterial enzymes in rats induced colon cancer by 1,2-dimethylhydrazine. Twenty milligrams per kilogram body weight of 1,2-dimethylhydrazine was administered subcutaneously once a week for the first 15 weeks and then discontinued. Ginger (50 mg/kg body weight/per day, oral) was given at the initiation and also at the postinitiation stages of carcinogenesis to 1,2-dimethylhydrazine-treated rats. The animals were killed at the end of 30 weeks. The macroscopic findings in the colon and the incidence of tumors were recorded in each group, and the activity of beta-glucuronidase and mucinase was estimated in the tissues and fecal contents of rats. After a total experimental period of 32 weeks (including 2 weeks of acclimatization), tumor incidence was 100% in 1,2-dimethylhydrazine-treated rats. The incidence of cancer as well as the number of tumors in the colon was significantly reduced both in the initiation and postinitiation stages of carcinogenesis on ginger administration. The activities of bacterial enzymes beta-glucuronidase (proximal colon, distal colon, intestines, liver and colon contents) and mucinase (colon and fecal contents) were significantly elevated in 1,2-dimethylhydrazine-treated rats as compared with the control rats. The increase in beta-glucuronidase activity may augment the hydrolysis of glucuronide conjugates, liberating the toxins, while the increase in the mucinase activity may enhance the hydrolysis of the protective mucins in the colon. Ginger administration to 1,2-dimethylhydrazine-treated rats significantly decreased the incidence and number of tumors as well as the activity of beta-glucuronidase and mucinase. Thus, ginger has a chemopreventive and anticarcinogenic effect against 1,2-dimethylhydrazine-induced colon cancer by virtue of its ability to lower the activities of the microbial enzymes beta-glucuronidase and mucinase.

1,2-Dimethylhydrazine↗

PubMed1996

Exon-specific DNA hypomethylation of the p53 gene of rat colon induced by dimethylhydrazine. Modulation by dietary folate.

Folate deficiency enhances colorectal carcinogenesis in dimethylhydrazine-treated rats. Folate is an important mediator of DNA methylation, an epigenetic modification of DNA that is known to be dysregulated in the early stages of colorectal cancer. This study investigated the effect of dimethylhydrazine on DNA methylation of the colonic p53 gene and the modulation of this effect by dietary folate. Sprague-Dawley rats were fed diets containing 0, 2, 8, or 40 mg of folate/kg of diet. Five weeks after diet initiation, dimethylhydrazine was injected weekly for fifteen weeks. Folate-depleted and folate-replete control animals did not receive dimethylhydrazine and were fed the 0- and 8-mg folate diets, respectively. The extent of p53 methylation was determined by a quantitative HpaII-polymerase chain reaction. In exons 6 and 7, significant p53 hypomethylation was observed in all dimethylhydrazine-treated rats relative to controls (P < 0.01), independent of dietary folate. In exon 8, significant p53 hypomethylation was observed only in the dimethylhydrazine-treated folate-depleted rats compared with controls (P = 0.038) and was effectively overcome by increasing levels of dietary folate (P = 0.008). In this model, dimethylhydrazine induces exon-specific p53 hypomethylation. In some exons, this occurs independent of dietary folate, and in others, increasing levels of dietary folate effectively override the induction of hypomethylation in a dose-responsive manner. This may be a mechanism by which increasing levels of dietary folate inhibit colorectal carcinogenesis.

Animals↗

PubMed1975

Autoradiographic studies on the distribution of 14C-1,2-dimethylhydrazine dihydrochloride and its effect on DNA synthesis in Swiss mice.

Light microscopic autoradiographic studies were made on the distribution of 14C-1,2-dimethylhydrazine dihydrochloride in Swiss mice and on the effect of 1,2-dimethylhydrazine dihydrochloride on DNA synthesis, using the 3H-thymidine incorporation technique. In the first study, 14C-1,2-dimethylhydrazine dihydrochloride was administered subcutaneously or orally. Large amount of silver grains were found in hepatocytes and substantially lower amount of silver grains observed in the endothelial cells and epithelial cells of colon. In the second study, repeated injections or oral administrations of 1,2-dimethylhydrazine dihydrochloride were given to mice which subsequently received 3H-thymidine treatment. A somewhat higher amount of thymidine incorporation in DNA was noted in the epithelial cells of the colon of subcutaneously and orally treated mice at two occasions and a substantially higher amount in the endothelial cells of blood vessels in liver of mice treated by both routes than in the corresponding controls. In three instances, however, the amount of incorporation decreased; in the hepatocytes and endothelium at 1 week and 24 hr, respectively, after oral treatment, and in the epithelium of the colon at 3 months, after subcutaneous administration. In the mice treated with 1,2-dimethylhydrazine dihydrochloride, a significantly high amount of 3H-thymidine incorporation was observed in the endothelial cells of blood vessel in liver from which tumors later arose, and somewhat high in the hepatocytes in which tumor did not develop. In the epithelial cells of colon, no apparent relationship can be seen between these events. No association was seen in the distribution of 14C-1,2-dimethylhydrazine dihydrochloride and tumor development in various cells.

Administration, Oral↗

PubMed1987

1,2-Dimethylhydrazine-induced alterations in colonic plasma membrane fluidity: restriction to the luminal region.

Recently, work in this laboratory has shown that changes in the 'dynamic' component of fluidity, lipid composition and phospholipid methylation activity of distal colonic brush-border membranes could be detected after administration of 1,2-dimethylhydrazine to rats of the Sherman strain for 5-15 weeks, i.e., before the development of colon cancer. The present experiments were therefore conducted to: determine whether similar 'premalignant' biochemical changes could be detected in basolateral membranes of Sherman rats treated with this agent; and clarify the relationship of these membrane changes to the malignant transformation process by examining the effect of 1,2-dimethylhydrazine on these biochemical parameters in colonic antipodal plasma membranes of rats of the Lobund-Wistar strain. This particular strain of rats has previously been shown to be total resistant to the induction of tumors by 1,2-dimethylhydrazine. The results of the present experiments demonstrate that similar biochemical alterations could not be detected in the colonic plasma membranes prepared from either strain of rat treated with 1,2-dimethylhydrazine. These data support the contention that the prior biochemical membrane alterations noted in brush-border membranes of 1,2-dimethylhydrazine-treated animals are, in fact, related to the malignant transformation process and, furthermore, are confined to the luminal surface of distal colonic epithelial cells.

1,2-Dimethylhydrazine↗

PubMed1988

Cellular proliferation in proximal and distal rat colon during 1,2-dimethylhydrazine-induced carcinogenesis.

Sequential changes in proliferative parameters in proximal and distal colonic crypts were studied during 1,2-dimethylhydrazine-induced carcinogenesis using [3H]thymidine autoradiography as a probe. 1,2-dimethylhydrazine (20 mg/kg) and vehicle (ethylenediaminetetraacetic acid) control rats received weekly s.c. injections for 20 wk. All animals received a pulse of [3H]thymidine before death at weeks 2, 6, 10, 16, 22, 26, or 30. In addition, 8 animals unexposed to 1,2-dimethylhydrazine or vehicle served as baseline controls. Dramatic regional differences were noted in the baseline controls. Crypt length, labeling index, and proliferative zone size were all significantly greater distally than proximally (p less than 0.05), whereas the labeling index of the proliferative zone tended to be enhanced proximally. During 1,2-dimethylhydrazine treatment the crypt length, labeling index, and proliferative zone size increased in both regions. As these parameters changed in parallel, the differences between proximal and distal colon did not change significantly during carcinogenesis. Actual tumor formation did differ, however, with tumors appearing earlier and in greater abundance in the distal colon. These findings show similar proliferative changes in both the proximal and distal colon during 1,2-dimethylhydrazine treatment and indicate that the enhanced baseline proliferative state of the distal colon compared with the proximal colon must be considered in the process of tumor formation.

1,2-Dimethylhydrazine↗

PubMed1989

1,2-Dimethylhydrazine-induced alterations in N1-acetylspermidine levels in rat distal colonic mucosa: effects of 2-difluoromethylornithine.

Recently, our laboratory has demonstrated that N1-acetylspermidine levels were increased in the distal colonic mucosa of rats administered 1,2-dimethylhydrazine for 15 and 26 weeks. In order to further explore the possible role of this acetylated polyamine in the malignant transformation process induced by this carcinogen, groups of rats were subcutaneously injected weekly with dimethylhydrazine (20 mg/kg body wt.) or diluent for 5, 10, 15 and 26 weeks +/- 1% 2-difluoromethylornithine in the drinking water. The latter agent, an irreversible inhibitor of ornithine decarboxylase, has previously been shown to inhibit colonic tumor formation in this experimental model. At each of these time periods, rats from each group were killed, their proximal and distal colonic mucosa harvested and examined, and compared with respect to polyamine levels, including N1-acetylspermidine, as well as the activities of ornithine decarboxylase, S-adenosylmethionine decarboxylase, spermidine N1-acetyltransferase and polyamine oxidase. The results of these experiments demonstrated that: (1) N1-acetylspermidine levels in the proximal colonic segment of all animals were similar at each time point; (2) N1-acetylspermidine levels were also similar in the distal colons of all animals at 5 and 10 weeks. At 15 weeks, however, the level of N1-acetylspermidine was increased in the dimethylhydrazine-treated distal colonic segment secondary to increases in the activity of spermidine N1-acetyltransferase; and (3) at 26 weeks, the level of this acetylated polyamine remained higher in dimethylhydrazine-treated distal 'uninvolved' colonic mucosa and was markedly elevated in colonic tumors; (4) co-administration of difluoromethylornithine decreased the elevated levels of N1-acetylspermidine to control values in the distal colons of animals treated with carcinogen for 15 and 26 weeks; and (5) difluoromethylornithine markedly reduced the number of tumors induced by dimethylhydrazine in the distal but not proximal colonic mucosa at 26 weeks.

1,2-Dimethylhydrazine↗

PubMed1992

Alterations in protein kinase C in 1,2-dimethylhydrazine induced colonic carcinogenesis.

Protein kinase C activity and the profile of protein kinase C isozymes alpha, beta, and gamma were examined in subcellular fractions of 1,2-dimethylhydrazine induced colonic adenocarcinomas, surrounding uninvolved colonic mucosa and colonic mucosa from age matched control rats. Responsiveness of colonic mucosal protein kinase C to phorbol dibutyrate induced translocation of the enzyme from the soluble to the particulate cell fraction was also assessed. Although total protein kinase C and specific activities of soluble and particulate enzymes were higher in colonic mucosa of carcinogen treated rats which developed tumors than corresponding values of control mucosa, the subcellular distribution of enzyme activity was not different between uninvolved colonic mucosa of 1,2-dimethylhydrazine treated rats and colonic mucosa of age matched control rats. Thus, evidence for activation of the protein kinase C system of mucosa of the carcinogen treated rats was lacking. Exposure of colonic mucosa from control rats to phorbol dibutyrate induced a clear translocation of enzyme activity from the soluble to the particulate fraction. By contrast, no change in subcellular distribution of protein kinase C activity was noted on exposure of colonic mucosa from 1,2-dimethylhydrazine treated rats to phorbol dibutyrate. Immunoblotting of subcellular fractions of colonic mucosa from control and 1,2-dimethylhydrazine treated rats demonstrated the presence of protein kinase C alpha, but no detectable beta and gamma forms. Total protein kinase C activity and the specific activity of protein kinase C in soluble and particulate fractions was significantly lower in adenocarcinomas compared to uninvolved surrounding mucosa. In contrast to results obtained with colonic mucosa from control and 1,2-dimethylhydrazine treated rats, adenocarcinomas expressed predominantly the beta form of protein kinase C. The alpha form represented less than 10% of the total detectable immunoreactivity in adenocarcinomas. The alterations in protein kinase C isoenzyme expression in tumors and loss of responsiveness of premalignant mucosa to phorbol dibutyrate may be involved in the process of malignant transformation.

1,2-Dimethylhydrazine↗

PubMed1974

Morphological and biochemical effects of 1,2-dimethylhydrazine and 1-methylhydrazine in rats and mice.

Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes including nucleolar microsegregation and changes in the endoplasmic reticulum and mitochondria. 1-Methylhydrazine caused little morphological change in the liver. Tumours of the colon and kidney and also massive cystic hyperplasia of the liver were found in some of the rats and tumours of the anal margin and kidney in some of the mice, following single doses of 1,2-dimethylhydrazine. Incorporation of amino acids into rat liver proteins was inhibited by 1,2-dimethylhydrazine, which also caused disaggregation of hepatic polysomes. No effects on hepatic protein synthesis by 1,1-dimethylhydrazine or 1-methylhydrazine were observed. Similarities between the effects of 1,2-dimethylhydrazine, cycasin and dimethylnitrosamine are discussed.

Animals↗

PubMed1974

The alkylation of nucleic acids of rat and mouse in vivo by the carcinogen 1,2-dimethylhydrazine.

1,2-Dimethylhydrazine, in contrast to 1-methylhydrazine, is a potent carcinogen for the colon in rats and mice. 1,2-[(14)C]Dimethylhydrazine was administered to rats and mice in doses which are carcinogenic following a single dose in the former species, or carcinogenic on repeated administration in the latter species, and the rate of (14)CO(2) exhalation was measured. Exhalation of (14)CO(2) was also studied after administration of single doses of 1-[(14)C]methylhydrazine to mice. Incorporation of radioactivity into the nucleic acids of a variety of organs was found at a time after injection (about 6 h) when (14)CO(2) production from both compounds was virtually complete. Methylation of nucleic acids of liver and colon, as indicated by the formation of 7-methylguanine, was observed after treatment with 1,2-dimethylhydrazine and to a smaller extent by a factor of about 10 after treatment with 1-methylhydrazine. Less than 1% of a single dose of 1,2-[(14)C]dimethylhydrazine was excreted in the bile of rats as determined by chemical and radioactivity assays. The similarities of the biological and biochemical actions of 1,2-dimethylhydrazine with those of some nitroso compounds and of cycasin (methylazoxymethanol glucoside) are emphasized.

Alkylation↗

PubMed1998

Dietary maltitol decreases the incidence of 1,2-dimethylhydrazine-induced cecum and proximal colon tumors in rats.

Maltitol is fermented in the colon due to only partial hydrolysis in the small intestine. In the present study, we examined effects of dietary maltitol on dimethylhydrazine-induced intestinal tumor in rats. In experiment 1, rats were fed a fiber-free diet or diets supplemented with 1 or 5 g/100 g maltitol for 27 wk. Each group of rats was injected with dimethylhydrazine or vehicle alone for the first 14 wk of the experimental period. Maltitol supplementation at 1 g/100 g of the diet significantly reduced tumor incidence in the cecum and the 5% supplement reduced tumor incidence in both the cecum and proximal colon in dimethylhydrazine-treated rats. In experiment 2, we investigated the effect of the 1 g/100 g maltitol diet on the short chain fatty acid concentrations in cecal contents of placebo and dimethylhydrazine-treated rats. Intake of the 1 g/100 g maltitol diet doubled (P < 0.05) the concentration of butyrate but did not affect acetate or propionate in the cecal contents. These results suggest that dietary maltitol has a protective effect against dimethylhydrazine-induced tumors in rat cecum and proximal colon and that butyrate produced by bacterial fermentation of maltitol in the cecum may be involved in the protection.

1,2-Dimethylhydrazine↗

PubMed1983

Metabolism of the carcinogen 1,2-dimethylhydrazine by isolated human colon microsomes and human colon tumor cells in culture.

Human colon microsomes catalyze the metabolism of the model colon carcinogen 1,2-dimethylhydrazine. Activity appears to be distributed in a gradient towards the lower end of the colon. Highest activities were observed for microsomes prepared from the descending segment of the colon with the transverse segment exhibiting lower activities, while the ascending segment showed the lowest rate of metabolism. Dimethylhydrazine metabolism in each segment is inhibited significantly by inhibitors of the cytochrome P-450-dependent mixed function oxidase system. Microsomes prepared from a human colon tumor cell also catalyze the metabolism of 1,2-dimethylhydrazine. Metabolic activity in the cell line can be induced two-fold by treatment of cells with phenobarbital and three-fold by treatment of the cells with phenobarbital plus hydrocortisone. These results show that human colon activates 1,2-dimethylhydrazine and suggest that the human colon may be capable of activating other carcinogens in situ.

1,2-Dimethylhydrazine↗

PubMed1986

The role of sphingomyelin synthetase and sphingomyelinase in 1,2-dimethylhydrazine-induced lipid alterations of rat colonic plasma membranes.

Recently, our laboratory, utilizing the 1,2-dimethylhydrazine model of colonic adenocarcinoma, demonstrated alterations in the 'dynamic component' of fluidity in brush-border membranes prepared from distal colonocytes of rats administered this agent for 5, 10 and 15 weeks, i.e., before the development of colon cancer. Furthermore, changes in the sphingomyelin content and sphingomyelin/phosphatidylcholine molar ratio of these membranes appeared, at least partially, to be responsible for these fluidity alterations. In an attempt to elucidate the mechanism(s) involved in these dimethylhydrazine-induced lipid changes, in the present studies the activities of sphingomyelin synthetase and magnesium-dependent neutral sphingomyelinase, enzymes involved in the synthesis and degradation of this phospholipid, respectively, were examined and compared in distal colonic brush-border membranes prepared from rats after 5, 10 or 15 weeks administration of dimethylhydrazine or diluent. The results of these studies demonstrate that alterations in both these enzymatic activities can be detected after administration of dimethylhydrazine and appear to, at least in part, be responsible for the changes in membrane sphingomyelin composition noted previously. These results as well as a discussion of their possible serve as the basis for the present report.

1,2-Dimethylhydrazine↗