[Mitomycin C-DNA adduct detection in rat organs and human liver].
Mitomycin C-DNA adduct formation was detected in rat organs and also in human tissues by 32P-postlabeling assay. The adduct levels were 1-4 adduct/ 10(8) nucleotides in the human liver after 20 mg of mitomycin C by intra-artery administration and which level was higher comparing with the levels in the rat liver after 10 times more dosages of mitomycin C administration by intra-venous injection. The levels in the human liver were maintained at least 56 days after administration. Organ-specific differences of adduct levels were observed in rat experiments: the adduct levels of liver, lung and kidney were stable but rapidly decreased in stomach and colon. These results, which were obtained from the experiments using the normal parts of each organs may indicate that the drug effectivity for adduct formation was sufficient with smaller dose in the stomach and colon, but disappeared quickly, mean while, the drug effectivity was undergoing in relatively high levels for longer periods in the liver lung and kidney. The analysis of human liver samples may suggest that the selective intra-artery injection induced stronger drug effectivity for adduct formation in human organs.
Kato
S
S
First Dept. of Surgery, Nippon Medical School, Japan.
Onda
M
M
Tokunaga
A
A
Yoshiyuki
T
T
Matsukura
N
N
Kim
D Y
DY
Tajiri
T
T
Yamashita
K
K
D000328:Adult; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000188:drug therapy; D018736:DNA Adducts / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000737:chemistry*; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D018736:DNA Adducts; D016685:Mitomycin