Disease relevance of as-Dimethylhydrazine

• Hamsters given DMH (25 mg/kg body weight s.c.), once a week for 3 weeks, showed ACF induction in the colon after 10 weeks, but there was no difference between the NAT2r and NAT2s hamsters [1].
• Mice receiving chronic DMH treatment showed a dose-dependent hyperplasia confined to the proliferative zone, with a parallel increase in mitotic and 3H-TdR-labelled cells and significant suppression of splenic NK activity [2].
• Long-term administration of DMH was more toxic to F-344 rats than to SD animals, and the toxicity was potentiated by reductions in the micronutrient composition of the diet [3].
• Soy molasses, which contains soy isoflavones, did not have an effect on colon cancer carcinogenesis in DMH-treated rats [4].
• In addition, an approximately equal number of animals challenged with DMH were fed daily, until the end of the study, 2 x 10(10) Lactobacillus casei subsp. rhamnosus strain GG starting three weeks before DMH administration or after the ninth weekly injection [5].

High impact information on as-Dimethylhydrazine

• However, CloA but not CleA prevented the DMH-induced reduction of splenocyte CD4/CD8 (T-helper cells to cytotoxic lymphocytes) ratio [6].
• CloA inhibited DMH induced genotoxic damage in mucosa cells of the distal colon compared with Cont as investigated by single-cell microgel electrophoresis assay [6].
• The crypt cell proliferation index induced by DMH (Cont/NaCl: 10.0+/-0.7%; Cont/DMH: 19.9+/-1.0%; P<0.001) was significantly decreased by CleA (15.7+/-0.7%; P<0.001) and CloA intervention (11.9+/-0.4%; P<0.001) [6].
• In the two congenic hamster lines we also studied the induction of ACF with 1,2-dimethylhydrazine (DMH) treatment, a colon carcinogen not metabolized by NAT2 [1].
• Weekly injections of dimethylhydrazine (DMH) (25 mg/kg), or azoxymethane (AOM) (8 mg/kg) to young adult male CDI mice for 1-2 months produced generalized intestinal crypt hyperplasia, which we measured in duodenum in terms of number of interphase and mitotic cells present in crypts [7].

Chemical compound and disease context of as-Dimethylhydrazine

• Finally, a stimulation of NK activity with Poly I:C treatment in DMH-treated mice caused regression of the DMH-induced hyperplasia [2].
• PURPOSE:: We examined the effects of treadmill-running training on the induction of aberrant crypt foci (ACF), which is the first step of colon cancer induction, in the colonic mucosa of rats injected with 1,2-dimethylhydrazine (DMH) [8].
• At the end of the experiment, the diet group administered DMH and high cholesterol (2% CH plus 0.25% CA) developed colon adenoma at 50% of incidence in pathological examination, but no colon adenoma formed in the rats treated with high cholesterol alone [9].
• The in vivo effect of E2 on DMH-induced colorectal cancer was studied in four groups of ovariectomized female rats: (I) untreated control, (II) E2 treated, (III) DMH treated, and (IV) combined E2 and DMH treated [10].

Biological context of as-Dimethylhydrazine

• The order of Cu(II)-mediated DNA damage (1,2-dimethylhydrazine greater than monomethylhydrazine approximately 1,1-dimethylhydrazine) was not correlated with the order of methyl free radical (.CH3) generation during Cu(II)-catalyzed autoxidation (monomethylhydrazine greater than 1,1-dimethylhydrazine much greater than 1,2-dimethylhydrazine) [11].
• It is supposed that a non-carcinogenic agent like cholesterol may potentiate the carcinogenicity of DMH in rats via an increase of lipid peroxidation and decrease in the activity of peroxidase in the target organ [9].
• Treatment with DMH significantly decreased the expression of the p53 transgene both in the ileum (from 18% to 100%) and in the colon (from 10% to 52%) [12].
• Evaluation of murine lymphocyte membrane potential, intracellular free calcium, and interleukin-2 receptor expression upon exposure to 1,1-dimethylhydrazine [13].

Anatomical context of as-Dimethylhydrazine

• In concurrent studies, 1,25(OH)2D3 was administered (s.c., 400 ng/rat) prior to, together with and after DMH challenge and the activity of ornithine decarboxylase (ODC), a growth-related DMH-induced enzyme, was determined in colonic cytosols [14].
• There were no detectable effects of DMH per se 15 weeks after the last injection (or in the presence or absence of tumors) on T-lymphocyte response to PHA or on NKCA [15].
• The highest frequency of micronucleated polychromatic erythrocytes (MPCE) and a dose-response relationship between erythropoietin doses and MPCE frequency were seen 30 hr after injection of 1,1-dimethylhydrazine (DMH) to mice administered 24 hr previously with erythropoietin [16].
• Enzymatic CAT activity was determined in the ileum and colon 8 weeks later after the final injection of DMH [12].

Associations of as-Dimethylhydrazine with other chemical compounds

• Simultaneous determination of hydrazine, methylhydrazine, and 1,1-dimethylhydrazine in air by derivatization/gas chromatography [17].
• To further explore the effects of these dietary regimens on immune function, rats were fed diets containing 20% safflower or coconut oil, with or without cholesterol (1%) and cholic acid (0.3%), for 35 weeks during which time they were given DMH [15].
• Treatment with DMH induced a highly significant increase in DNA damage in sucrose- and lactulose-fed rats [18].
• Thus, the induction of colonic tumors by DMH and successful kidney autotransplants can be substantially abrogated by synchronous treatment with indomethacin [19].
• The reaction of the tert-butyl imido complex Ti(N(t)Bu)Cl2(py)3 with either 1,1-dimethylhydrazine or N-aminopiperidine again resulted in the formation of hydrazido-bridged dimeric complexes, namely Ti2(mu-eta2,eta1-NNMe2)2Cl4(py)2 (5, structurally characterized) and Ti2[mu-eta2,eta1-NN(CH2)5]2Cl4(py)2 (6) [20].

Gene context of as-Dimethylhydrazine

• This FMO protein catalyzed thiobenzamide S-oxidation, and NADPH oxidation associated with the S- or N-oxidation of thiourea, N,N-dimethylaniline, trimethylamine, imipramine, chlorpromazine, N,N-dimethylhydrazine, thioacetamide as substrates [21].
• Effect of 1,1-dimethylhydrazine on lymphoproliferation and interleukin 2 immunoregulatory function [22].
• Feeding the high-fat diet and DMH treatment caused higher activity of hepatic iNOS [23].
• High pressure oxygen (HBO) and 1,1-dimethylhydrazine (UDMH) both cause grand mal seizures, brain glycogen degradation, and inhibition of glutamic acid decarboxylase (GAD) [24].

Analytical, diagnostic and therapeutic context of as-Dimethylhydrazine

• The mutagenic effect of 1,1-dimethylhydrazine (UDMH) was studied in the liver perfusion/cell culture system [25].
• Effect of 1,1-dimethylhydrazine (UDMH) on Corynebacterium parvum-associated immunosuppression in mice [26].
• The animals were given a subcutaneous injection of the carcinogen, 1,2-dimethylhydrazine (DMH), on d 4 [23].
• Lack of carcinogenicity of daminozide, alone or in combination with its contaminant 1,1-dimethylhydrazine, in a medium-term bioassay [27].
• For the comet assay, peripheral blood samples were collected 4 h after the last DMH treatment [28].

References