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A photochemical mechanism for single-strand cleavage of DNA is proposed in which a photoexcited intercalator transfers an electron to an externally bound cosensitizer. Once formed, the oxidized intercalator oxidizes an adjacent base, creating a charge-separated complex from which reactions leading to cleavage of the sugar-phosphate backbone occur in competition with back electron transfer. Using ethidium bromide (EB) as the intercalator and methyl viologen (MV) as the externally bound cosensitizer, a 10-fold enhancement in the rate of single-strand break formation was found in pBR322 DNA over that for EB alone using 488-nm excitation. The rate of cleavage correlated with the amount of MV bound to DNA. In accord with the expected redox properties of the one-electron-oxidized EB and the DNA bases, cleavage occurs selectively at guanines. Although the reaction proceeds in nitrogen-purged solutions, the rate of cleavage in air-saturated solutions was enhanced 2-fold. Treatment of irradiated samples with alkali leads to a 2-fold increase in the yield of single-strand breaks. These results support a mechanism in which cleavage occurs by selective oxidation of guanines in DNA, initiated by photochemical cosensitized electron transfer from intercalated EB to externally bound MV, and may provide a basis for the development of light-activated base-selective DNA cleaving agents.

The resource-based relative-value scale (RBRVS) is a measure of relative levels of resource input expended when physicians produce services and procedures. It is a function of the physician's work input, the opportunity cost of specialty training, and the relative practice costs for each specialty. This paper presents resource-based relative values (RBRVs) for selected procedures of four major specialties--family practice, internal medicine, general surgery, and thoracic and cardiovascular surgery. We compare RBRVs with current charges and find several general patterns. Invasive procedures are typically compensated at more than double the rate of evaluation-and-management services, when both consume the same resource inputs. Imaging and laboratory procedures fall between invasive and evaluation-and-management services. We analyze the financial implications of the RBRVS by developing a simple model and simulating the effects of an RBRVS-based fee schedule on physicians' revenues in various specialties. We use Medicare data to perform the simulation under the "budget-neutral" assumption. Results show that an RBRVS-based fee schedule affects specialties differently. The average family practitioner could receive 60 percent more revenue from Medicare, whereas the average ophthalmologist could lose 40 percent of current revenues. The effects on other specialties fall between these two.