Reaction of 7,12-dimethylbenz(a)anthracene with DNA of fetal and maternal rat tissuesin vivo

Abstract

Pregnant BD‐IX rats (21st day of gestation) received a single IV injection (15 mg/kg) of tritiated 7,12‐dimethylbenz(a)anthracene (DMBA), a dose known to induce a high incidence of nervous‐system tumors in the offspring. The animals were killed 12 h later and hydrocarbon‐deoxyribonucleoside products from DNA of maternal and fetal tissues were separated on Sephadex LH‐20 columns eluted with a 20–100% methanol gradient. Concentrations of the major DMBA‐DNA adduct varied considerably, with highest values in maternal intestine, liver and lung, followed by spleen, kidney and brain. In fetal intestine and liver, concentrations were 34% and 16% lower than in the respective maternal organs whereas the reaction with cerebral DNA was 2 1/2 times higher in fetuses than in the pregnant mother. This indicates that there is no significant placental barrier to DMBA or DMBA metabolites involved in DNA binding and that rat fetuses participate in the metabolic formation of the ultimate carcinogen.