Specific Carcinogenic and Teratogenic Effects of ‘Indirect’ Alkylating Methyl and Ethyl compounds, and their Dependency on Stages of Ontogenic Developments

Druckrey, H.

doi:10.3109/00498257309151524

Cited by 166 publications

(51 citation statements)

References 54 publications

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“…Within the rat models, the 2 factors that appear to most heavily influence the type of neoplasm produced are chemical entity (16,21,22) and time of exposure (16,20,21 (20)(21)(22) whereas N-ethyl-Nnitrosourea (ENU) appears to be the best-documented chemical for the induction of nephroblastomas (21,22 (14). With respect to time of exposure, most methylating agents are poor transplacental carcinogens (16), but they are much more potent in the immature rat kidney (20)(21)(22).…”

Section: Experimental Animalsmentioning

confidence: 99%

“…DMPT is also a transplacental carcinogen, reportedly affecting the central nervous system most commonly with concurrent production of some renal neoplasms (16); unfortunately, histopathological descriptions and photomicrographs of the neoplasms induced were not included. Because genotoxic chemicals may induce neoplasms and terata by the same mechanism (6,7), it is interesting when a tissue/organ (e.g., urogenital system) is a transplacental carcinogenic target but is remarkably resistant to the teratogenic effects of such chemicals.…”

Section: Introductionmentioning

confidence: 99%

“…3,3-Dimethyl-1-phenyltriazene (DMPT) is a nethylating agent that is mutagenic ( 11,28,41,46), teratogenic (18, 34), and carcinogenic (16,40). As a teratogen, DMPT has a remarkable lack of phase specificity in that the targets are not significantly influenced by administration on different days of gestation (Frank, unpublished data).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Renal Transplacental Carcinogenicity of 3,3-Dimethyl-1-Phenyltriazene in Rats: Relationship of Renal Mesenchymal Tumor to Congenital Mesoblastic Nephroma and Intralobar Nephrogenic Rests

et al. 1992

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Exposure of rat embryos to 3,3-dimethyl-1-phenyltriazene (DMPT) results in numerous malformations, but the urogenital system is not affected. In contrast, exposure of rat fetuses to DMPT has been reported to result in renal neoplasms, which were not further classified. To better understand this discrepancy in organotropism of the teratogenic and transplacental carcinogenic processes, the present study was undertaken to characterize the neoplasms induced in rat fetuses exposed to DMPT in utero. Renal neoplasms and persistent mesenchyme were observed in 19.2 and 11.5%, respectively, of the offspring of rats treated with 1 mg DMPT/ kg body weight intraperitoneally on gestation days 16, 18, and 20. The majority of these renal lesions were observed in females. The renal neoplasms were mixtures of various types of mesenchymal tissue derivatives including smooth muscle and fibrous connective tissue. These neoplasms would be classified as renal mesenchymal tumors in rats. Brain neoplasms (numerous types), compound odontomas, and micrognathism were observed predominantly in male offspring from the same group. This treatment also resulted in decreased body weights, increased incidence of sudden loss of body weight, tremors and ataxia, and hypoplastic testes. Exposure to single intraperitoneal doses of DMPT on gestation day 20 did not produce a classic dose-response pattern: Minimal effects were observed with 10 mg DMPT/kg (occasional renal mesenchymal tumors and brain neoplasms), marked effects were observed with 30 mg DMPT/kg (lower incidence rate of most of the alterations observed with 1 mg/kg on gestation days 16, 18, and 20), and no effects were observed with 60 mg DMPT/kg. DMPT administered intraperitoneally at 1 mg/kg body weight on gestation days 16, 18, and 20 is an animal model of transplacental chemically induced renal neoplasms, which provide lesions with similarities to both intralobar nephrogenic rests and congenital mesoblastic nephroma of humans. Why the kidney is a carcinogenic target and not a teratogenic target remains unknown.

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Section: Experimental Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Renal Transplacental Carcinogenicity of 3,3-Dimethyl-1-Phenyltriazene in Rats: Relationship of Renal Mesenchymal Tumor to Congenital Mesoblastic Nephroma and Intralobar Nephrogenic Rests

et al. 1992

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“…Transplacental tumorigenesis has been studied with dimethylnitrosoamine 2 , 3,3-dimethyl-1-phenyltriazene 8 , azo-and azoxyethan 9 , and ENU [1][2][3][4][5][6][7] . Almost all of these studies, however, have reported their tumorigenesis in selected organs or tissues, such as the renal tumors 10-14 , including nephroblastoma [1][2][3]15 , and neuroectodermal tumors [5][6][7][16][17][18][19] .…”

Section: Discussionmentioning

confidence: 99%

Transplacental Carcinogenicity of N-Ethyl-N-Nitrosourea in Sprague-Dawley Rats

et al. 2004

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N-Ethyl-N-nitrosourea (ENU) is known to induce a wide spectrum of tumors in various organs in adult experimental animals. The renal and neuroectdermal tumors are known as representative lesions by transplacental exposure to ENU in the offspring animals. However, little information is available about tumorigenicity in other organs and tissues in offspring when their mother animals are treated with ENU during gestation. Thus, the purpose of this study was to evaluate the effects of transplacentally treated-ENU on the various organ tumorigenicity in offspring rats. ENU was injected intraperitoneally to female Sprague-Dawley (SD) rats with a single dose at 50 mg/kg on the 18th day of gestation. After spontaneous delivery, 44 male and 64 female offspring, including moribund and dead after birth, were subjected to the evaluation of carcinogenicity. At the 54th to 55th week of birth, all surviving offspring were euthanized under ether anesthesia for histopathology. ENU showed a wide spectrum of transplacental tumorgenesis in the kidney, central nervous system, peripheral nervous system, thyroid gland, and teeth. The tumors of the thyroid and teeth were characteristic in particular in this study. The thyroid tumors included various histopathological types (follicular cell adenoma and adenocarcinoma, C-cell adenoma and carcinoma, squamous cell carcinoma, and fibroma). As a characteristic tumor of the teeth, ameloblastic odontoma was detected in 3 (one male and 2 females) of 108 offspring. In conclusion, the results indicate that the transplacental exposure of a single ENU dose induces various types of thyroid gland tumors and odontogenic tumors as well as the renal or neuroectodermal tumors in rat offspring. (J Toxicol Pathol 2004; 17: 7-16)

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“…4 Increasing attention is being paid to the chemistry of nitrosamines owing to the toxicity 5 and carcinogenic, 6 mutagenic, 7 and teratogenic 8 properties of these compounds. In more recent times, since the discovery of the amazing biological properties of nitric oxide there has been a large interest in the chemistry of S-nitrosothiols, these can act as possible vasodilators, anti-platelet aggregation agents etc.…”

Section: Introductionmentioning

confidence: 99%

Kinetic study of an autocatalytic reaction: nitrosation of formamidine disulfide

et al. 2008

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The reaction kinetics for the acid nitrosation of formamidine disulfide (FDS) show an autocatalytic behavior that arises from the fact that the thiocyanate ion formed as a product acts as a powerful catalyst for the nitrosation reaction. In the presence of added nucleophiles the suppression of the autocatalytic route results from competition for the nitrous acid between the added halides and the thiocyanate anion, which is formed as a reaction product. Analysis of the kinetic data enabled extraction of the bimolecular rate constants, Kinetic results are consistent with the attack on the nitrosating agent as the rate limiting step, i.e., the nitrosation of FDS behaves in a similar manner to the nitrosation of an amine. Rather different behavior is found for other substrates with an imino moiety adjacent to an amino nitrogen, such as the guanidines, which react by a mechanism in which the rate limiting step is the reorganization of the nitrosated substrate.

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Specific Carcinogenic and Teratogenic Effects of ‘Indirect’ Alkylating Methyl and Ethyl compounds, and their Dependency on Stages of Ontogenic Developments

Cited by 166 publications

References 54 publications

Renal Transplacental Carcinogenicity of 3,3-Dimethyl-1-Phenyltriazene in Rats: Relationship of Renal Mesenchymal Tumor to Congenital Mesoblastic Nephroma and Intralobar Nephrogenic Rests

Renal Transplacental Carcinogenicity of 3,3-Dimethyl-1-Phenyltriazene in Rats: Relationship of Renal Mesenchymal Tumor to Congenital Mesoblastic Nephroma and Intralobar Nephrogenic Rests

Transplacental Carcinogenicity of N-Ethyl-N-Nitrosourea in Sprague-Dawley Rats

Kinetic study of an autocatalytic reaction: nitrosation of formamidine disulfide

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