Investigation into the pharmacodynamics of the carcinogen N-nitrodimethylamine.
N-Nitrodimethylamine (NTDMA) was found to be a carcinogen of the nasal mucosa leading to aesthesioneuroepitheliomas in BDVI rats. N-Nitromethylamine (NTMA), a product of the oxidative metabolism of NTDMA, was also carcinogenic, leading to neurogenic tumours of the lumbar region of the spine. The 100,000 X g supernatant of both liver and nasal mucosa contains an enzyme capable of reducing NTDMA to N-nitrosodimethylamine (NDMA). In the microsomal fraction of both organs, NTDMA is oxidized to formaldehyde. The fractions from nasal mucosa have a higher capacity than the corresponding liver fractions to both oxidize and reduce NTDMA. NDMA was detected in blood and urine from rats treated with NTDMA. The elimination of NTDMA from blood occurs biphasically, with an initial half-life of 3.5 min.
Hassel
M
M
German Cancer Research Center, Heidelberg.
Frei
E
E
Scherf
H R
HR
Wiessler
M
M
D000693:Anaerobiosis; D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics*; D004123:Dimethylamines / Q000493:pharmacokinetics*; D004128:Dimethylnitrosamine / Q000378:metabolism; D005260:Female; D006207:Half-Life; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000139:chemically induced; D009574:Nitro Compounds / Q000493:pharmacokinetics*; D009669:Nose Neoplasms / Q000139:chemically induced; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D004123:Dimethylamines; D009574:Nitro Compounds; C013962:dimethylnitramine; D004128:Dimethylnitrosamine