Reaction of 7,12‐dimethylbenz(a)anthracene with DNA of fetal and maternal rat tissues in 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, liverand 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.

In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis

“…This compound is also known to induce nervous-system tumors in the offspring of rats treated at the end of gestation. DNA binding in the brain was indeed more than twice as high in the fetus as compared to the pregnant mother, whereas the DNA binding in liver or intestine was higher in the mother [57]. The bladder carcinogen O·aminoazotoluene (Table 16) gives rise to the highest CBI for DNA of the bladder.…”

CYP1A1 and CYP1B1 in Blood-Brain Interfaces: CYP1A1-Dependent Bioactivation of 7,12-Dimethylbenz(a)anthracene in Endothelial Cells

“…Both CYP1A1 and 1B1 are known to metabolically activate PAHs to reactive intermediates (Shimada et al, 1996). PAH-DNA adducts have previously been detected in brain homogenates of 7,12-dimethylbenz(a)anthracene (DMBA)-treated rats (Doerjer et al, 1978) and benzo(a)pyrene (B(a)P)-treated rats, mice, rabbits, and monkeys (Das et al, 1985;Stowers and Anderson, 1985;Lu et al, 1993). The cellular localization of protein/DNA adducts in the brain following exposure to PAHs has however not been reported.…”

Differing Levels of Excision Repair in Human Fetal Dermis and Brain Cells

“…Recent studies by Budunova and Belitsky (1980) showed that repair of both UV and N-methyl-N-nitro-N-nitroso-guanidine was lower in cells isolated from human fetal liver than dermis. Other studies in rodents have shown that fetal tissues are more sensitive to the carcinogenic effects of DNA damaging agents (Swenberg et al, 1972;Doerjer et al, 1978;Rice et al, 1978) than are adult tissues.…”