In vivo Conversion of Phenmetrazine into its N-Nitroso Derivative

Greenblatt, Melvin; Kommineni, V. R. Choudari; E, Conrad; Wallcave, Lawrence; Lijinsky, William

doi:10.1038/newbio236025a0

Cited by 20 publications

(4 citation statements)

References 6 publications

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“…Because of the toxicity of nitrosamines and the ubiquity of their precursors, information on the mechanisms of N-nitrosation and factors affecting the synthesis of such toxicants under natural conditions are of considerable significance. There is ample evidence that secondary amines and nitrite combine nonbiologically in solutions at low pH values, as in the spontaneous formation of di-n-propylnitrosamine (9,22). The nonbiological production of such compounds in acid solutions requires that appropriate controls be included in any study of a possible microbial contribution to the genesis of these hazardous compounds.…”

Section: Discussionmentioning

confidence: 99%

Microbial Formation of Nitrosamines In Vitro

Ayanaba¹,

Alexander²

1973

Applied Microbiology

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Section: Discussionmentioning

confidence: 99%

Microbial Formation of Nitrosamines In Vitro

Ayanaba¹,

Alexander²

1973

Applied Microbiology

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“…Although unknown factors could affect possible MNP production in man when piperazine and food containing residual nitrite are taken together, a limited intake of nitrite-containing foods in individuals receiving piperazine seems prudent. It also appears important to evaluate possible hazards due to the intragastric formation of N-nitroso compounds from other drugs which contain nitrosatable groups, e.g., secondary amines (11,14,17), tertiary amines (18), alkylureas (14), and N-alkylcarbamates (14).…”

Section: Discussionmentioning

confidence: 99%

Dose-Response Studies With Concurrent Administration of Piperazine and Sodium Nitrite to Strain A Mice2

Greenblatt¹,

Mirvish²

1973

JNCI: Journal of the National Cancer Institute

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Male strain A mice were given 0.69-18.75 g piperazine/kg Food and 0.05-2.0 g sodium nitrite (NaN02)/liter drinking water For 20-25 weeks, and were killed 10-13 weeks later. The yield of lung adenomas was significantly greater than in untreated controls when as liHle as 0.69 9 piperazine/kg plus 1.0 9 NaNOdliter, or 6.25 9 piperazine/kg plus 0.25 9 NaN02/liter, were given. A maximum of 30.7 adenomas/mouse more than the controls was observed with 6.25 9 piperazine/kg plus 2.0 9 NaN02/liter. Mononitrosopiperazine (MNP) at 34.5 mg/liter drinking water induced 3.8 adenomas/mouse more than the controls. Negative results were obtained with NaN02 alone, piperazine alone, 12.3 9 sodium nitrate (NaNOa)/liter alone, or 12.3 9 NaNOa/liter plus 18.75 9 piperazine/kg. The laHer result indicated that nitrate was not reduced to nitrite under conditions suitable For reaction with the piperazine. When the piperazine concentration was raised From 0.69-18.75 g/kg Food in 3 threefold increments at a constant level of nitrite, the adenoma yield was increased between successive doses by ratios of 1.4 to 2.5. A ratio of 3.0 was predicted by application of the kinetic equation for MNP formation (adenoma yield was assumed to be proportional to MNP production). When the nitrite concentration was raised from 0.25-2.0 g/Iiter water in 3 twofold increments at a constant level of piperazine, the adenoma yield was increased by ratios of

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“…A number of investigators have shown that nitrosamines can be formed in vivo from ingested amines and nitrite (Sander et al, 1968;Greenblatt et al, 1972; Mysliwy et al, 1974). Moreover, the same tumors are produced in experimental animals that are fed amine plus nitrite as in those fed the corresponding nitrosamine (Sander and Burkle, 1969; Taylor and Lijinsky, 1975; Ivankovic and Preussman, 1970).…”

mentioning

confidence: 99%