Summary
The cytostatic drug procarbazine has previously been shown to be a potent transplacental neurotropic carcinogen in rats. Following a single IP administration of (14C-methylprocarbazine (110 mg/kg) on day 22 of gestation, methylation products with cellular DNA were determined in fetal and maternal rat organs. The concentration of the major adduct N7-methylguanine was highest in the maternal liver (224 μmol/mol guanine). Fetal and nonhepatic maternal tissues exhibited significantly lower levels, but differed little from each other. In brain, lung, intestines, and placenta the O 6-methylguanine/N7-methylguanine ratio was close to 0.11, indicating that procarbazine, like other methylating carcinogens, initiates malignant transformation via methyldiazonium hydroxide as the ultimate reactant. Following a single dose of (14C-methyl)procarbazine to newborn animals, methylpurine values were 30–60 times lower than after prenatal administration. This suggests that DNA alkylation in nonhepatic tissues occurs by systemic distribution of a proximate carcinogen formed in the adult rat liver.
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Dedicated to Professor Hermann Druckrey on the occasion of his 80th birthday
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Wiestler, O.D., Kleihues, P., Rice, J.M. et al. DNA methylation in maternal, fetal and neonatal rat tissues following perinatal administration of procarbazine. J Cancer Res Clin Oncol 108, 56–59 (1984). https://doi.org/10.1007/BF00390973
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DOI: https://doi.org/10.1007/BF00390973