Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dimethylhydrazines”

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 163 records · Page 9Linked to original sources
PubMedDate not supplied

Activity of 1,2-dimethylhydrazine in the mouse bone marrow micronucleus assay using a triple- and a single-dosing protocol.

In the present study the ability of 1,2-dimethylhydrazine (DMH) to induce micronuclei in mouse bone marrow erythrocytes was investigated using 2 different dosing regimens. DMH caused an increase in micronuclei in both male and female mice following single administration and sampling after 24 h. The effect was more pronounced in female than in male animals. Triple administration of DMH at concentrations corresponding to 80, 40 and 20% of the median lethal dose (MLD) did not increase the incidence of micronuclei in either sex. Small increases in micronucleus incidence were observed after triple dosing at 100% of the MLD value. These results suggest that a future micronucleus protocol should include animals of both sexes and single and repeated administration of the test substance.

1,2-Dimethylhydrazine↗
PubMed1996

Selective induction of micronuclei in the rat/mouse colon and liver by 1,2-dimethylhydrazine: a seven-tissue comparative study.

1,2-Dimethylhydrazine (DMH) was administered to both genders of mice and rats by oral gavage for 3 days. Twenty-four hours later, an assessment of the incidence of micronucleated cells was made in the bone marrow and sections of the gastrointestinal tract. An increase in micronucleated cells was observed in the colon of both genders of both species of rodent. Negative responses were observed in the forestomach, stomach, duodenum, intestine of both species. The bone marrow micronucleus assays were essentially negative, but the absence of a precise definition of the MTD precludes a definitive conclusion from being drawn. These results are consistent with the selective carcinogenicity of DMH to the colon of the rodent GI-tract. DMH is also known to be carcinogenic to rat and mouse liver and, although it is known to induce micronuclei in the hepatocytes of rats, no such data exist for the mouse. Consequently, mice were administered DMH on 13 successive days, followed by 2/3 partial hepatectomy and assessment of micronucleated hepatocytes. A strong positive liver micronucleus assay response was observed. Thus, DMH selectively induces micronuclei in the colon and liver of rats and mice, consistent with its carcinogenicity to these two tissues. No qualitative differences between the genders was observed in any of the assays. These results indicate that the assessment of genetic toxicity in rodents should not rely solely on assays made in bone marrow.

1,2-Dimethylhydrazine↗
PubMed1986

In vitro DNA and nuclear proteins alkylation by 1,2-dimethylhydrazine.

The methylating carcinogen 1,2-dimethylhydrazine (DMH) CAS 540.73.8 is highly organ-specific and, under certain experimental conditions, produces a high incidence of adenocarcinoma in the colon of rodents. We have tried to assess the possibility that part of the organ-specifity in the carcinogenic effect of DMH could be attributed to its metabolism by specific microsomal enzymes. In particular, we compared the in vitro effects of DMH in the presence of either colon or liver microsomes from animals that had been treated with microsomal enzyme inducers. V79 Chinese hamster cells were used as the target to evaluate the damage to the genetic material, as judged by (1) formation of adducts of DNA bases and (2) amino acid modifications in nuclear proteins using [Me-14C]DMH and appropriate analytical detection systems. Our results tend to support the above postulated hypothesis.

1,2-Dimethylhydrazine↗
PubMed1991

Down-regulation of protein kinase C activity in 1,2-dimethylhydrazine-induced rat colonic tumors.

Recent studies by our laboratory have indicated that alterations in protein kinase C activity may be involved in the early stage(s) of malignant transformation in the 1,2-dimethylhydrazine model of colonic adenocarcinoma. In order to further evaluate the possible role of protein kinase C in this multistage process, rats were given subcutaneous weekly injections of this procarcinogen (20 mg/kg body weight) or diluent for 26 weeks. One week after receiving the last injection, animals were killed and control colonic tissue, tumor tissue and tissue at least 1 cm away from these tumors ('uninvolved mucosa') were harvested. The activity and distribution of protein kinase C in the cytosolic and membrane fractions of these preparations as well as their 1,2-diacylglycerol mass were then examined and compared. The results of these studies demonstrated that: (1) total protein kinase C activity was reduced by approximately 35% and 60%, respectively, in the 'uninvolved' colonic mucosa and tumors of carcinogen-treated rats compared to their control counterpart values; (2) in the 'uninvolved' mucosa, this decrease in total activity was secondary to a decrease solely in cytosolic protein kinase C, whereas, in tumors both membrane and cytosolic activities were reduced; and (3) 1,2-diacylglycerol mass was significantly increased in colonic tumors versus control values. Based on these findings, it would appear that alterations in the cellular distribution and total activity of protein kinase C, possibly secondary to increases in 1,2-diacylglycerol mass, may also play a role in the latter stage(s) of malignant transformation in this experimental model.

1,2-Dimethylhydrazine↗
PubMed1984

Effect of Metamucil on tumour formation by 1,2-dimethylhydrazine dihydrochloride in mice.

The effect of the plant cellulose metamucil on the tumorigenicity of 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was studied in random-bred Swiss mice. Three groups of mice, which were 5, 6 and 6 weeks old at the beginning of the experiment, were given the following treatments: (1) metamucil (20%, w/w) in powdered diet for their lifespan; (2) 1,2-DMH, ten weekly subcutaneous injections at 20 mg/kg body weight; (3) combination of treatments given to groups 1 and 2. The administration of metamucil enhanced the appearance of colon tumours induced by 1,2-DMH in males only. Metamucil had no statistically significant effect on the development of tumours elicited by 1,2-DMH at seven additional sites. It was expected that a high amount of dietary fibre would inhibit carcinogenesis in the large intestine. Instead, metamucil increased the incidence of colon tumours induced by 1,2-DMH, although only in males.

1,2-Dimethylhydrazine↗
PubMed1988

DNA alkylation by 1,2-dimethylhydrazine in the rat large intestine and liver: influence of diet and enzyme induction.

Male Wistar rats were fed a semi-purified diet (MID - minimal inducing diet) with or without addition of 50 ppm of beta-naphthoflavone (BNF) for 1 week. After 1 week the rats were dosed with 20 mg/kg of 1,2-dimethylhydrazine (DMH) subcutaneously and killed at various time intervals from the injection. Enzyme levels were determined in microsomal and cytosolic fractions prepared from the liver and the intestinal mucosa. Feeding of BNF for 1 week caused a 6.5-fold increase of 7-ethoxyresorufin (7-ERR) deethylase in the colon as compared to the controls, but did not alter glutathione (GSH) content nor glutathione-S-transferase (GSHST) activity. Hepatic cytochrome P-450 and 7-ERR deethylation were not significantly altered by feeding of BNF at this concentration, whereas GSH and GSHST were increased by a factor of 1.6 and 2, respectively. In the DMH-dosed rats, O6-methylguanine was formed to a greater extent in the BNF-treated colon than in the controls at 1, 12 and 24 h, whilst N7-methylguanine levels were essentially the same in the induced and uninduced rats. No significant difference was found in the degree of hepatic DNA alkylation at any time points. As shown by our results, the nature of the diet would appear to be able to modulate the rate of metabolic activation of DMH and its binding to DNA in the target organ.

1,2-Dimethylhydrazine↗
PubMed1981

Degenerative behavior of epithelial cells in the colonic crypt of the mouse following administration of colonic carcinogen, 1,2-dimethylhydrazine.

The degenerative behavior of cells following administration of 1,2-dimethylhydrazine was analyzed in its target organ, the distal colon of the mouse. Within 3-6 h after carcinogen treatment, an increasing number of epithelial cells in the proliferative compartment of the crypt degenerated. Degenerating cells were present most frequently as phagosomes in the neighboring epithelial cells, and infrequently as pyknotic nuclei being extruded from the epithelial lining in the crypt. Epithelial cells prelabeled with [3H]thymidine degenerated first, followed by those not prelabeled, indicating that the carcinogen-induced degeneration of cells occurred after passage of cells through the DNA synthesis phase.

1,2-Dimethylhydrazine↗
PubMed1981

Parameters for detection of mutagenesis of 1,2-dimethylhydrazine using an in vitro Bacillus subtilis system.

Parameters for detection of mutagenesis of 1,2-dimethylhydrazine (DMH) using a Bacillus subtilis microbial assay are defined. His+ and his met mutations were induced in B. subtilis TKJ6321 in the absence of rat liver S-9 Mix. This B subtilis mutant showed a greater sensitivity to this chemical than did Salmonella typhimurium TA1535. Protein-binding studies with bovine serum albumin showed the capacity for DMH to bind non-specifically to protein. S-9 mix from Aroclor pretreated animals appeared to decrease the mutagenic response. Kinetics of mutagen stability were also shown, thereby demonstrating the need for more complete investigation of known chemical carcinogens which give negative results in the Ames bioassay alone.

1,2-Dimethylhydrazine↗
PubMedDate not supplied

Inhibition of carcinogenicities of 1,2-dimethylhydrazine and azoxymethane by pyrazole.

Inhibitory effects of pyrazole on the carcinogenicities of 2 large-bowel carcinogens, 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM), were examined, because our previous study revealed that pyrazole completely inhibited the induction of mutations by these carcinogens in the host-mediated mutation assay. ICR male mice were treated subcutaneously once a week for 20 weeks either with DMH or with AOM. Pyrazole was given orally to mice 2 h before treatment with the carcinogen. Pathological examinations were conducted 36 weeks after the first treatment. Treatment with DMH or AOM alone induced colorectal and/or anal tumorigenic lesions in 92% (23/25) mice of the DMH group and 100% (22/22) mice of the AOM group. By contrast, none of the animals in the combined treatment groups (carcinogen + pyrazole) developed those tumors. On the other hand, 50% (13/26) of mice treated with DMH alone and 78% (18/23) of mice treated with AOM alone developed vascular tumors. Pretreatment of mice with pyrazole reduced the percentage of mice bearing this type of tumor to about 30% of that in the carcinogen group with either carcinogen. These results clearly show that pyrazole has the ability to inhibit carcinogenicities of DMH and AOM, especially for the colorectum and anus, and indicate that the inhibition studies of mutation induction in vivo provide a useful tool for the screening for inhibitors of the carcinogenicities of DMH and AOM.

1,2-Dimethylhydrazine↗
PubMed1983

Effect of Konjac mannan on 1,2-dimethylhydrazine-induced intestinal carcinogenesis in Fischer 344 rats.

The effect of Konjac mannan (KM) on 1,2-dimethylhydrazine (DMH-induced intestinal carcinogenesis was studied in male F344 rats. Rats were fed a diet containing 5% KM at 5 weeks of age. At 6 weeks of age, all animals were given a weekly intraperitoneal injection of 20 mg DMH/kg body wt for 13 weeks and autopsied 13 weeks after the last injection of DMH. The weight gain was lower in rats fed the KM diet than in rats fed the control diet throughout the experiment (P less than 0.05). The incidence of DMH-induced colon tumors was lower in animals fed the KM diet compared to animals fed the control diet (P less than 0.05). The number of colon adenocarcinoma per animal was also lower in animals fed the KM than in animals fed the control diet (P less than 0.05). However, the incidence of tumors of the small intestine did not significantly differ between the groups fed the KM and control diets. The present study demonstrated that colon tumorigenesis induced by DMH in F344 rat was inhibited by maintaining the KM diet.

1,2-Dimethylhydrazine↗
PubMed1984

The relationship of colonic carcinogenesis and hepatic vascular tumors induced by subcutaneously injected-1,2-dimethylhydrazine dihydrochloride in specific pathogen free mice.

1,2-Dimethylhydrazine dihydrochloride (DMH) is one of the most reliable carcinogens for experimental colonic carcinogenesis. In order to evaluate the biological significances of target organ specificity of DMH-induced carcinogenesis, specific pathogen free (SPF) BALB/c mice were injected subcutaneously with DMH for 30 weeks, and were studied pathologically for tumor development of various organs. The data showed that colon tumor developed only at 2% of these mice. However, it produced 100% incidence of malignant endotheliomas and angiosarcomas of blood vessels and these tumors selectively appeared in the liver. There were no overt foci of primary vascular tumors in the heart, lung, kidney, muscle as well as spleen. This tumor model may reveal that the organ specificity of the carcinogenic activity with DMH could be converted, possibly depending upon the bacterial flora in the intestines, and very suitable for the investigation of implications of intestinal bacteria on the colonic and vascular tumorigenesis.

1,2-Dimethylhydrazine↗
PubMed1985

Effect of dietary seaweed preparations on 1,2-dimethylhydrazine-induced intestinal carcinogenesis in rats.

Nineteen preparations from 8 species of edible seaweeds, sodium alginate and cellulose powder were incorporated into a basic diet in proportions ranging from 0.05% to 2.0%, and used as experimental diets. Experimental rats were fed these diets and controls were fed the basic diet for 12 weeks. All rats also received the carcinogen, 1,2-dimethylhydrazine, during above period. After 20 weeks, all rats were autopsied and the incidence of intestinal tumors induced were examined. There was a significant decrease in incidence in rats fed 6 preparations from Eisenia bicyclis, Laminaria angustata, L. angustata var. longissima and Porphyra tenera (P less than 0.05).

1,2-Dimethylhydrazine↗
PubMed1986

Correlation between incidence of 1,2-dimethylhydrazine-induced colon carcinomas and DNA damage in six genetically different mouse strains.

Mice from strains with different susceptibility to the colon-specific carcinogen 1,2-dimethylhydrazine (DMH) were tested for DNA damage in liver, kidney and colon after administration of the compound at a dosage that has been reported to induce a high incidence of adenocarcinoma in the colon of rodents. DNA breaks were evaluated from their elution rate constant according to the alkaline elution technique. We found that 4 h after administration of the carcinogen there was a substantial and comparable DNA damage in liver and kidney of all strains examined. Conversely, colon DNA damage was hardly above control levels in the carcinogen-resistant strains. The highest DNA damage was detected in the most susceptible strain and was slightly lower in the two other susceptible strains. We propose that the extent of DNA breakage in a target organ could be one of the factors determining organ-specific and strain-specific susceptibility to DMH.

1,2-Dimethylhydrazine↗
PubMed1989

Lack of modifying effects of linolic acid hydroperoxides and their secondary oxidative products on combined 7,12-dimethylbenz[a]anthracene and 1,2-dimethylhydrazine-initiated mammary gland, ear duct and colon carcinogenesis in female Sprague-Dawley rats.

Effects of hydroperoxides, autoxidation products of linolic acid (HPO) and secondary oxidative products of HPO (SOP) (5% each in diet) were examined in female Sprague-Dawley rats. HPO and SOP administration was carried out during or subsequent to two injections of dimethylhydrazine (DMH) (40 mg/kg body wt s.c.), and a single i.g. dose of 7,12-dimethylbenz[a]anthracene (DMBA) (50 mg/kg body wt). No significant differences in the incidences of tumors in the mammary gland, colon, ear duct and hematopoietic system associated with HPO or SOP treatment were evident, during or after carcinogen exposure. The present results therefore indicate that the environmental contaminants, HPO and SOP, lack any potential for modification of mammary gland or colon carcinogenesis under the conditions of the investigation.

1,2-Dimethylhydrazine↗
PubMed1990

Effects of naturally occurring antioxidants on combined 1,2-dimethylhydrazine- and 1-methyl-1-nitrosourea-initiated carcinogenesis in F344 male rats.

The effects of treatment with naturally occurring antioxidants, selenium, beta-carotene, ferulic acid, esculin and eugenol during the promotional phase of tumor development were investigated in male F344 rats pre-treated with 1,2-dimethylhydrazine (DMH) and 1-methyl-1-nitrosourea (MNU). Animals were given 3 subcutaneous injections of DMH at a dose of 40 mg/kg body wt. within 1 week and then were injected with MNU i.p. at a dose of 20 mg/kg body wt. 2 times per week, for 2 weeks. Thereafter, the rats were maintained on diet containing either 0.2% beta-carotene, 2 ppm selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52, surviving rats were killed and complete histological examinations were performed. Administration of eugenol enhanced the development of both hyperplasia and papillomas in the forestomach. Although treatment with beta-carotene tended to decrease the incidence and number of large intestinal carcinomas, beta-carotene, selenium, esculin and eugenol all decreased the incidence of kidney nephroblastomas, the differences were not statistically significant. The results thus showed that eugenol exerts promoting activity for forestomach carcinogenesis while the other antioxidants might have weak organ-specific inhibitory effects under these experimental conditions.

1,2-Dimethylhydrazine↗
PubMed1991

Effects of dietary fat on hepatic microsomal metabolism of 1,2-dimethylhydrazine.

The present study was designed to examine the effects of different high fat diets on the liver microsomal metabolism of aminopyrine (AMP) and 1,2-dimethylhydrazine (DMH). Male Sprague-Dawley rats were fed either a low fat (5% corn oil) or high fat (20%) diets containing either corn oil, menhaden oil or beef tallow for a period of up to 9 months. Liver microsomes were assayed for N-demethylase activity for both AMP and DMH substrates at 2 weeks, 1, 6 and 9 months of diet only, and also after 1, 2, 5 and 10 DMH treatments (20 mg/kg body weight). The menhaden oil-fed group had consistently higher AMP demethylase activity, which increased up to 6 months and then declined. Beef tallow-fed rats had the highest DMH demethylase activity following DMH, but this decreased by 10 treatments. These data indicate that type and amount of dietary fat affects microsomal metabolism of carcinogens, which may enhance tumor initiation.

1,2-Dimethylhydrazine↗
PubMed1991

Modifying effect of ascorbic acid and sodium ascorbate on the promoting stage of uterine sarcomogenesis induced in CBA mice by 1,2-dimethylhydrazine and estradiol-dipropionate.

Administration of estradiol-dipropionate (EP) after the cessation of 1,2-dimethylhydrazine (DMH) treatment increased the incidence of uterine sarcomas in CBA mice from 32.5 (DMH alone) to 62.5%. Ascorbic acid (AA) (0.3% in drinking water) given simultaneously with EP decreased the tumour incidence to 35%. Sodium ascorbate did not exert an inhibiting effect. AA inhibited the increase of uterine weight produced in mice by EP and did not influence the growth of mouse transplantable uterine sarcomas. The mechanisms of the antiestrogenic effects of AA are discussed.

1,2-Dimethylhydrazine↗
PubMed1991

The thalidomide analog, EM 12, enhances 1,2-dimethylhydrazine-induction of rat colon adenocarcinomas.

Young male Sprague-Dawley rats in 3 groups were fed a basal diet supplemented with 0.10 wt. % each of thalidomide and its imide-analog of much higher teratogenicity, EM 12. Following an induction period of 17 days on the diets, all animals were injected subcutaneously with 1,2-dimethylhydrazine at 20 mg/kg for a total of 20 weekly doses and killed on week 18 after the 20th injection. The total number of colon adenocarcinomas and their occurrence in the proximal and distal portions for the thalidomide-treated rats were similar to those of the respective controls. However, the EM 12-fed group elicited statistically significant increases both in the total and ascending colon-based adenocarcinomas as compared with the control findings, in keeping with its greater teratogenicity and embryotoxicity. The numbers of small intestinal adenocarcinomas were equally higher in the imide-fed groups in contrast to the control frequency.

1,2-Dimethylhydrazine↗