-transparent.png){kind=logo}
Distribution, excretion, and metabolism of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea (ACNU) in healthy rats and mice or tumor-bearing mice were studied with the 14C label in each of two positions of the molecule, the ethylene and pyrimidine moieties. After iv injection of 4 mg/kg of ACNU-14C, radioactivity was distributed widely and disappeared rapidly from the body. The half-life of intact ACNU in rat plasma was about 12 minutes. In both animal species, 72%-95% of the radioactivity was excreted into urine within 24 hours. Early dissociation of renal clearance rate was observed between pyrimidine-14C and ethylene-14C, the former being more rapidly excreted than the latter. Ethylene-14C of ACNU was distributed into tumor tissues of X-5563 plasmacytoma-bearing mice, and a tumor level of radioactivity was observed to be twofold higher than the blood level at 3 hours after injection. The concentrations of several metabolites in plasma and urine were determined. Among these compounds, we found an intramolecular carbamoylating product of ACNU. These results suggest that the isocyanate derived from ACNU does not react with any biologic macromolecules, and that the chloroethyl moiety of ACNU has a very important role in the manifestation of the antitumor activity.
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
June 1983,
Gan to kagaku ryoho. Cancer & chemotherapy,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
August 1988,
Gan to kagaku ryoho. Cancer & chemotherapy,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
October 1993,
Gan to kagaku ryoho. Cancer & chemotherapy,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
January 1994,
Journal of neuro-oncology,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
September 2006,
Journal of neuro-oncology,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
August 1982,
Cancer,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
January 1981,
No shinkei geka. Neurological surgery,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
October 1978,
Gan,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
November 1987,
Cell biology international reports,
M Tanaka, and
T Nishigaki, and
E Nakajima, and
S Totsuka, and
K Nakamura
July 1979,
Cancer research,
