NITROZOALKILMOCHEVINA — group of oncogenous nitroso compounds.
where R is the radical (methyl, ethyl, propyl, butyl, phenyl etc.).
Are most studied a nitrozometilmochevin (NMM) and a nitrozoetilmochevin (NEM) — yellowish crystals, water soluble and polar organic solvents. They are unstable in alkaline condition, and nek-ry N. quickly decay in the neutral environment. At the same time education of the alkylating agent happens the quicker, than above pH of the environment. Half-life of NEM at pH 4,0 makes 190 hours, and NMM — 125 hours; at pH 9,0 half-life of NEM is reduced to 3 min., and NMM — makes apprx. 2 min. After intravenous administration of NEM its content in blood decreases twice every 5 — 6 min.; NMM in 15 min. after intravenous administration to rats is not found in blood. N are capable to alkylate nucleinic to - you are in vivo and in vitro (see. Acylation ). DL 50 at intravenous administration to rats of NMM and NEM makes respectively 110 and 240 mg/kg. The N renders both the local, and systemic damaging action, degree to-rogo is defined by the rate of decay of N. in an organism. The toxic effect at N.'s action is caused by defeat of the fabrics having high mitotic activity, napr, marrow, an adenoid tissue, a mucous membrane of intestines.
N are the strongest mutagens (see), and unlike dialkylnitrosamines their mutagen properties in bacterial systems are shown without preliminary incubation in the presence of microsomes of a liver.
N possess strong embriotoksichesky and teratogenic action. Embriotoksichesky action is shown at N.'s introduction in the first third of pregnancy, teratogenic — is preferential during the second third and the beginning of the last third of pregnancy.
The N has oncogenous effect on many types a lab. animals, at various ways of introduction and even at single introduction. To oncogenous action of N. the nervous system is highly sensitive, especially at introduction in the second half of pregnancy and in the perinatal period. At rats of a tumor of a head, spinal cord and peripheral nerves arise at transplacental influence of NEM in a dose of 1 mg/kg, at a dose of 20 mg! kg — in 100% of cases. The rats who received during pregnancy of NEM in a dose 60 — 150 mg/kg have tumors of a uterus and a vagina. Neurogenic tumors at action of NEM most often arise at rats; hamsters have smaller oncogenous sensitivity, at to-rykh hl develop. obr. tumors of peripheral nerves. NEM and NMM cause also tumors of kidneys, the hemopoietic system and other bodies. Nitrozobutilmochevina causes in rats of a tumor of the hemopoietic system, mammary glands, c. N of page, gullet; at mice — a tumor of the hemopoietic system; at hamsters — a tumor of a peripheral nervous system. Nitrozofenilmochevina induces at rats of sarcoma on site introductions. Streptozototsin [N-d-glyuko-zil-(2)-] Ch-sh1trozometilmochevina] in rats causes tumors of kidneys, and in hamsters — a tumor of a liver. At rats of a nitrozometilatsetilmochevin induces tumors of a ferruterous stomach, the central and peripheral nervous system; nitrozometil-(2 benzothiazolyl) urea — tumors of a prestomach and kidneys.
N can be formed in an organism; e.g., at introduction by an animal ethyl - or methylurea in combination with sodium nitrite at them arises the tumors typical for influence of NEM or NMM.
Thanks to strong cytotoxic action nek-ry N. (especially NMM and its derivatives) use for treatment of malignant tumors (see. Nitrozometilmochevina ). A row H. is applied in pilot studies.
During the work with N. it is necessary to take measures for prevention of their hit on skin, mucous membranes for prevention of complications and went. - kish. path.
Bibliography: Alexandrov V. A. Uterine, vaginal and mammary tumors induced by nitrosoureas in pregnant rats, Nature (Lond.), v. 222, p. 1064, 1969; it, Embryotoxic and teratogenic effects of chemical carcinogens, in book: Transplacental carcinogenesis, ed. by L. Tomatis a. U. Mohr, p. 112, Lyon, 1973; lARC monographs on the evalution of the carcinogenic risk of chemicals to humans, v. 17, Lyon, 1978; I vankovic S. u. Druck-r e y H. Transplacentare Erzeugung maligner Tumoren des Nervensystems. I Athyl-nitroso-harnstoff (ANH) an BD IX Ratten, Z. Krebsforsch., Bd 71, S. 320, 1968; M a-gee P. N., Montesano R. a. Preussmann R. N-nitroso compounds and related carcinogens, in book: Chemical carcinogenesis, ed. by Ch. E. Searle, p. 491, Washington, 1976; S w a n n P. F. a. Magee P. N. Nitrosamine-indueed carcinogenesis, Biochem. J., v. 110, p. 39, 1968.
V. S. Turusov.