Carcinogene Wirkung von Phenyl-nitroso-harnstoff

Preußmann, R.; Druckrey, H.; J, Bücheler

doi:10.1007/bf00524503

Cited by 24 publications

(10 citation statements)

References 9 publications

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“…Nonetheless, intrinsic alkylating reactivities of certain classes of alkylating agents have been helpful in rationalizing their biological reactivity, deleterious or otherwise. For example, Lawley & Brookes (1968) have shown that iodoacetamide, which gives a positive NBP test (Preussmann, et al, 1969), may be classified as a non-radiomimetic alkylating agent, since it does not react in wico with nucleic acids, but reacts preferentially with the thiol group of proteins. Also, Ostermann-Golkar, et al (1970) have, with some success, studied the mutagenic efficiency towards barley of the simple alkyl methanesulphonates in this way, and Bardos, Chmielewicz & Hebborn (1 969) have described the application of structure/activity studies in the development of nitrogen mustards for use in cancer chemotherapy-an area of study largely pioneered by Ross (1962).…”

Section: Discussionmentioning

confidence: 99%

“…I n some preliminary experiments with methyl methanesulphonate employing procedure A of Preussmann, et al (1969) at looo, reproducibility for reaction times of 60 min (A, conditions) and 10 min (A, conditions) were respectively poor and fair. Indeed, when a reaction time of 16 h was employed, the yield of coloured product was nil (six replicates).…”

Section: The Nitrobenzylpyridine Colour Reaction For Alkylating Agentsmentioning

confidence: 98%

“…8) causes only a fourto five-fold diminution in reactivity towards hydroxide ion, but about a ninetyfold diminution in reactivity towards the NBP reagent. From this example, and that of parathion which was tested by Preussmann, et al (1969) that the diethyl organophosphorus insecticides, as a class, will be characterized by comparatively higher reactivity at phosphorus with respect to that at carbon, when compared with their dimethyl analogues. One or two other comments on the results of the application of the NBP colour reaction are appropriate.…”

Section: T Redford and J Robinsonmentioning

confidence: 98%

“…Preussmann, et al (1969) tested more than 200 compounds by each of the procedures, A,, A, and B. Generally speaking, known alkylating agents gave a positive colour test under one set of conditions or the other (A or B) ; only a few (very reactive) compounds reacted under both sets of conditions.…”

Section: The Nitrobenzylpyridine Colour Reaction For Alkylating Agentsmentioning

confidence: 99%

“…Preussmann, et al (1969) found that esters of phosphorus acids give a positive response with procedure A, and a negative response with procedure B. Using a semi-quantitative scale based on the optical density of the coloured reaction product of + + + , + + , + and -, several organophosphorus insecticides were given the top + + + rating.…”

Section: The Nitrobenzylpyridine Colour Reaction For Alkylating Agentsmentioning

confidence: 99%

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The Alkylating Properties of Organophosphates

1972

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1. A brief introduction to the concept of alkylation is given, which discusses reaction mechanisms and reactivity, and includes an assessment of the susceptibility to alkylation of biologically-important molecules. 2.A semi-quantitative colour test for alkylating agents, with 4-(pnitrobenzyl) pyridine (NBP), has been modified to give a quantitative method for the determination of second-order rate constants, k,, for reaction at 37.5". These constants have been determined for dichlorvos, several other organophosphorus insecticides, and, for comparison, some known biological alkylating agents. 3.These results are discussed in relation to the extensive literature data pertaining to the chemical and biological reactivity of these compounds, and an assessment of the biological importance of the alkylating properties of dichlorvos and related organophosphorus insecticides has been made.4. Since dichlorvos is rapidly metabolized in mammals by esterases present at high activity in the liver and moderate activity in lung, spleen, kidney and blood plasma, the chances of its manifesting spontaneous deleterious biological alkylating activity are very low, and may even be zero. Structure/activity correlations suggest that this will also apply to other organophosphate insecticides, but not necessarily to simple alkyl phosphates such as trimethyl phosphate. Recently Lofroth, Kim & Hussain (1969) have made a preliminary in nitro evaluation of the alkylating properties of dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP), which has prompted them to draw comparisons between dichlorvos and the powerful alkylating agents and known mutagenic agents, methyl and ethyl methanesulphonates.Recently, too, the alkylating properties of some other organophosphorus insecticides have been demonstrated by subjecting them to the NBP (4-(p-nitrobenzy1)pyridine) colour test for alkylating agents (Preussmann, Schneider & Epple, 1969). Strong positive ( + + + ) responses, it was claimed, were given by methylparathion, Chlorthion, Metasystox, thiometon, malathion, Dipterex and Gusathion, and weak positive ( + + ) responses by parathion, ethion, sulfotepp and Systox. Preussmann, et al. (1969) also measured the alkylating properties of about 200 other compounds, including aliphatic and aromatic halogen compounds, lactones and sulphones, epoxides, ethylenimines, diazo and azo compounds, nitrosamines, nitrosamides, and esters of other strong acids. Noteworthy in the latter group were dimethyl sulphate and methyl methanesulphonate, which were given the same (semi-quantitative) top rating of + + + as that given to seven of the organophosphorus insecticides. I n view of this, a critical study of the NBP colour reaction has been made. XB . T Xenobiotica Downloaded from informahealthcare.com by Nyu Medical Center on 07/30/15 For personal use only.T h e first section of this review provides a brief introduction to the concept of alkylation. This is followed by an appraisal of the relevance of the results of the NBP colour test as an index of biological al...

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Section: Discussionmentioning

confidence: 99%

Section: The Nitrobenzylpyridine Colour Reaction For Alkylating Agentsmentioning

confidence: 98%

Section: T Redford and J Robinsonmentioning

confidence: 98%

Section: The Nitrobenzylpyridine Colour Reaction For Alkylating Agentsmentioning

confidence: 99%

Section: The Nitrobenzylpyridine Colour Reaction For Alkylating Agentsmentioning

confidence: 99%

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The Alkylating Properties of Organophosphates

1972

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Nitrosophenylurea 6268‐32‐2

2004

Sax's Dangerous Properties of Industrial Materials

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Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules

Miller

1981

Cancer

696

275

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Studies on a variety of chemical carcinogens have demonstrated that their ultimate reactive and carcinogenic forms are strong electrophiles. Some carcinogens, such as alkylating agents, are in their ultimate forms as administered, but most require metabolism to these active derivatives. The ultimate carcinogens react, usually non-enzymatically, with nucleophilic constituents in vivo. Of particular interest in regard to their possible importance in carcinogenesis have been the covalent interactions of these electrophilic reactants with cellular informational macromolecules, the DNAs, RNAs, and proteins. Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens. The nature of the carcinogen metabolite(s) involved in the promotion phase has not been determined, but there appears to be no requirement that they be electrophilic. The development of the concept of ultimate chemical carcinogens as strong electrophilic reactants is reviewed, especially with respect to the studies carried in the authors' laboratory.

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Carcinogene Wirkung von Phenyl-nitroso-harnstoff

Cited by 24 publications

References 9 publications

The Alkylating Properties of Organophosphates

The Alkylating Properties of Organophosphates

Nitrosophenylurea 6268‐32‐2

Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules

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