The three-dimensional structure of Escherichia coli 3-methyladenine DNA glycosylase II, which removes numerous alkylated bases from DNA, was solved at 2.3 A resolution. The enzyme consists of three domains: one alpha + beta fold domain with a similarity to one-half of the eukaryotic TATA box-binding protein, and two all alpha-helical domains similar to those of Escherichia coli endonuclease III with combined N-glycosylase/abasic lyase activity. Mutagenesis and model-building studies suggest that the active site is located in a cleft between the two helical domains and that the enzyme flips the target base out of the DNA duplex into the active-site cleft. The structure of the active site implies broad substrate specificity and simple N-glycosylase activity.

Rectal GISTs showed high rates of local recurrence regardless of the surgical procedure. Perioperative treatment with imatinib may improve outcomes.

No abstract

The distribution of ingested stable, lipophilic environmental pollutants in dams and their transfer to fetuses and sucklings were investigated in rats fed a diet containing a small amount (35.1 nmol/100 g diet) of hexachlorobenzene (HCB). In the first experiment, we examined the distribution of HCB in pregnant and nursing rats fed the HCB diet during pregnancy and lactation. Its transfer to their sucklings was also studied. On d 16 after parturition, HCB concentrations in the blood, and subcutaneous and perirenal fat of nursing rats fed the HCB diet during pregnancy and lactation were approximately 1/3.5, 1/15 and 1/2.8, respectively, those of pregnant rats fed the HCB diet only during pregnancy. On the other hand, the HCB concentrations in the blood, and subcutaneous and perirenal fat of sucklings were approximately 6, 29 and 15 times higher than those of their dams. Therefore, a large amount of HCB apparently was transferred from dams to suckling pups through the milk. In the second experiment, we fed dams the HCB diet only during pregnancy and determined the distribution of HCB in the pregnant rats and fetuses as well as in the nursing rats and suckling pups. The estimated amount of HCB transferred from a dam to her fetuses corresponded to about 0.39% of her total intake during pregnancy. The amount of HCB detected in nursing rats on d 16 after parturition was much smaller than that in the pregnant rats, suggesting that a large proportion of the HCB that accumulated during pregnancy disappeared from the organs and fat tissues during lactation. The HCB concentration in the stomach contents of suckling pups fed by the dams who had consumed HCB before parturition was highest on d 2 after birth and decreased gradually during the 16 d after birth. In the blood, liver and fat tissues of suckling rats, the HCB concentrations increased until 7 d after birth and then decreased gradually. We conclude that the HCB that accumulated in dams during pregnancy was transferred to their suckling pups through milk in the early days after birth.

No abstract