No abstract

Earlier work (Paul, T., et al. (2000) Biochemistry 39, 4129-4135) has demonstrated that the water soluble positively charged peroxyl radical, (H(2)N)(2)(+)CC(CH(3))(2)OO(*) ((+)AOO(*)), caused direct strand scission of the Escherichia coli plasmid supercoiled DNA, pBR 322, with ca. 50% scission occurring at a (+)AOO(*)/base pair (bp) ratio of 0.2. There was no measurable direct scission with a negatively charged peroxyl ((-)BOO(*)) at (-)BOO(*)/bp = 24, nor with a neutral peroxyl (COO(*)) at COO(*)/bp = 5. Base modification (BM) of the same DNA by the same peroxyls has now been investigated using four base excision repair (BER) glycosylases. At (+)AOO(*)/bp = 0.04, there is 10% direct strand scission, and the Fpg protein recognized an additional 25% BM, while endonuclease (Endo) IV recognized an additional 20% BM and the other two BER enzymes did not give statistically significant BMs. None of the BER enzymes showed BMs in the DNA treated with -BOO(*). However, Fpg and Endo IV showed that at COO(*)/bp = 3.4 there was a BM comparable to that observed at (+)AOO(*)/bp = 0.04. Thus, COO(*) radicals are only ca. 1.2% as reactive toward the DNA's bases as (+)AOO(*). These results underline the importance of Coulombic forces in DNA reactions. It is also proposed that (+)AOO(*) has a higher intrinsic reactivity in H-atom abstractions and electron transfer processes than (-)BOO(*) or COO(*) radicals.

Male rodents display greater systemic morphine antinociception than females which show their most marked effects during late diestrus or proestrus. Morphine (1-2.5 mug) antinociception on the tail-flick test elicited from the ventrolateral periaqueductal gray was examined across estrus phases in female relative to male rats. Morphine antinociception was greatest in magnitude and potency in males followed by females tested during the proestrus phases relative to estrus and met-diestrus. These data confirm morphine's systemic effects, implicate the ventrolateral periaqueductal gray in estrus phase-mediated effects, and underscore the control of the phase of the estrus cycle in examining sex differences in opioid antinociception.