Morphological and Biochemical Effects of 1,2-Dimethylhydrazine and 1-Methylhydrazine in Rats and Mice

Hawks, A.; Hicks, Rodney W.; Holsman, J. W.; Magee, P N

doi:10.1038/bjc.1974.217

Cited by 53 publications

(11 citation statements)

References 31 publications

(19 reference statements)

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“…At body temperature, methyl-azoxymethane is an unstable compound that undergoes decomposition spontaneously, giving rise to formaldehyde, water, nitrogen, and methyl diazonium, an alkylating agent that introduces a reactive carbonic ion capable of reacting with DNA, RNA, and proteins (Weisburger, 1971). The DMH carcinogenic activity therefore involves DNA methylation into colonic epithelial cells (Hawks et al, 1974). The methyl-azoxymethane also undergoes an enzyme-metabolizing process by the action of the alcohol dehydrogenase enzyme (present in the liver and colon, and at low concentrations in the jejunum and ileum), becoming methyl azoxy formaldehyde (Grab and Zedeck, 1977).…”

Section: Discussionmentioning

confidence: 99%

Effects of Moquiniastrum polymorphum ssp floccosum ethnolic extract on colorectal carcinogenesis induced by 1,2-dimethylhydrazine

Limeiras¹,

Oliveira²,

Pessatto³

et al. 2017

Genet. Mol. Res.

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ABSTRACT. The objective of this study was to evaluate the effect of Moquiniastrum polymorphum ssp floccosum ethanolic extract (MPEE) on 1,2 dimethylhydrazine (DMH)-induced colorectal carcinogenesis in mice. Forty-two male Swiss mice (Mus musculus) were subdivided into six groups (N = 7/group): negative control, DMH, MPEE, pre-treatment, simultaneous, and post-treatment. Results showed that MPEE has antigenotoxic potential on the tested protocols pre-and silmultaneous treatment, and the percent damage reductions (%DRs) were 81.88 and 93.12%, respectively. The micronucleus test demonstrated that MPEE has great antimutagenic activity, with %DRs higher than 77.09 in the associated groups. The aberrant crypt focus assay demonstrated anticarcinogenic potential of MPEE as the associated groups showed %DRs that ranged from 62.13 to 95.14%. The study shows that MPEE is nontoxic and has chemopreventive and anticarcinogenic activity, thus it may prove to be a promising medicinal plant in view of its demonstrated properties.

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Section: Discussionmentioning

confidence: 99%

Effects of Moquiniastrum polymorphum ssp floccosum ethnolic extract on colorectal carcinogenesis induced by 1,2-dimethylhydrazine

Limeiras¹,

Oliveira²,

Pessatto³

et al. 2017

Genet. Mol. Res.

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“…While the epithelial cells of the colonic mucosa are the main target of DMH genotoxicity with DMH inducing colorectal tumors in experimental animals, this xenobiotic is also a potent hepatocarcinogen [Hawks et al, 1974]. Regarding DMH, the capacity of alkylate DNA to induce oxidative stress [Swenberg et al, 1979], and alter the activity of the XMEs [Viswanathan et al, 1998] has also been reported.…”

Section: Model Mutagenmentioning

confidence: 99%

Modulatory activity of a Lactobacillus casei strain on 1,2‐dimethylhydrazine‐induced genotoxicity in rats

Villarini

Caldini

Moretti

et al. 2008

Environ and Mol Mutagen

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The present study was designed to investigate the putative antigenotoxic effects of supplementing the diet of rats treated with the colon carcinogen 1,2-dimethylhydrazine hydrochloride (DMH) with a Lactobacillus casei strain using an in vivo approach. The antigenotoxic response was evaluated in colon and liver cells using the alkaline comet assay. Since the balance between the bioactivation and detoxification metabolic pathways is crucial for the formation of toxic and genotoxic metabolites, alterations in the level of some xenobiotic metabolizing enzymes (XME) were studied in liver preparations. In the challenge group (L. casei + DMH), lactobacilli-supplemented diet, there was a decrease in the extent of DMH-induced DNA damage, especially in colon cells. Compared with control rats, there was less basal DNA damage in colon cells of rats fed on a lactobacilli-supplemented diet. These findings are the first to give clear evidence of DNA-protective effects of lactobacilli against basal DNA damage. Moreover, the chemopreventive effects were accompanied by changes in the activities of several XME. The observed decrease in the concentration of nonenzymatic antioxidants (i.e. GSH) and the reduced activity of enzymatic antioxidants (i.e., GST, GPx, and SOD) in liver could reflect an overall reduction in the level of oxidative stress in rats on a diet supplemented with the L. casei suspension compared with control rats (basal state). Thus, the concentrations of GSH and the activities of GST, GPx, and SOD could be downregulated by supplementing the diet with L. casei as a response to an improved antioxidant status.

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“…guanylate cyclase-cyclic GMP system and car cinogenesis since the effects are directly opposite within the group. On the other hand, hydrazine which stimulates the production of cyclic GMP increases DNA synthesis (1) in contrast to the inhibitors of guanylate cyclase, isonicotinic acid hydrazide, hydrazine sulfate and dimethylhydrazine, which have been shown to decrease DNA synthesis (4,8,10,19). Since the many studies noted earlier have linked cyclic GMP to cell growth and DNA, RNA, and general protein synthesis, the association between the effects of these four carcinogens on guanylate cyclase activity and DNA synthesis appears to be more than coincidental.…”

Section: Discussionmentioning

confidence: 99%

“…Hydrazine, a chemical carcinogen in tobacco and tobacco smoke (18), produces tumors in a variety of tissues (29). The substituted hydra zine, dimethylhydrazine, has been reported to induce colonic (7), kidney (10), and blood vessel tumors (28).…”

Section: Introductionmentioning

confidence: 99%

Effect of Hydrazine, Isonicotinic Acid Hydrazide, Hydrazine Sulfate, and Dimethylhydrazine on Guanylate Cyclase Activity

Vesely¹,

Rovere²,

Levey³

1978

Enzyme

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The chemical carcinogen hydrazine is a potent stimulator of guanylate cyclase. In the present investigation we found that three chemical carcinogens structurally related to hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine, decreased guanylate cyclase activity. It is of interest that hydrazine has been shown to increase DNA synthesis whereas isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine decrease DNA synthesis. The relationship, if any, linking the guanylate cyclase-cyclic GMP system to DNA synthesis and carcinogenesis remains to be explored.

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Morphological and Biochemical Effects of 1,2-Dimethylhydrazine and 1-Methylhydrazine in Rats and Mice

Cited by 53 publications

References 31 publications

Effects of Moquiniastrum polymorphum ssp floccosum ethnolic extract on colorectal carcinogenesis induced by 1,2-dimethylhydrazine

Effects of Moquiniastrum polymorphum ssp floccosum ethnolic extract on colorectal carcinogenesis induced by 1,2-dimethylhydrazine

Modulatory activity of a Lactobacillus casei strain on 1,2‐dimethylhydrazine‐induced genotoxicity in rats

Effect of Hydrazine, Isonicotinic Acid Hydrazide, Hydrazine Sulfate, and Dimethylhydrazine on Guanylate Cyclase Activity

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