Modification of DNA by mitomycin C in cancer patients detected by 32P-postlabeling analysis.
DNA adducts of mitomycin C (MMC) were detected by 32P-postlabeling analysis in both surgical specimens and an autopsy sample of the liver of patients with hepatocellular carcinoma who had received chemotherapy with MMC. Four kinds of adducts were detected in all 6 patients treated with MMC. These adducts had identical chromatographic mobilities to those of adducts in the liver of rats treated with MMC, but 1 additional adduct was detected in rat liver. In patients treated with MMC, about 3 adducts/10(8) nucleotides were found 4 days after MMC treatment, and 1 adduct/10(8) nucleotides 14 days after treatment and the latter level was maintained for up to 56 days. MMC-DNA adducts were also detected in peripheral blood leukocytes from a patient 1 and 7 days after MMC treatment, at levels of 1 and 0.6 adduct/10(8) nucleotides, respectively. These results suggest the tumor-initiating activity of MMC in humans.
Kato
S
S
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
Yamashita
K
K
Kim
T
T
Tajiri
T
T
Onda
M
M
Sato
S
S
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy; D016685:Mitomycin; D008937:Mitomycins / Q000009:adverse effects*; D051381:Rats
D004273:DNA, Neoplasm; D008937:Mitomycins; D016685:Mitomycin; D004247:DNA