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The induction of single-strand breaks (SSB) by two quantum processes in DNA is well established. We now report that biphotonic processes result in double-strand breaks (DSB) as well. pUC19 and bacteriophage M13 RF DNA were irradiated using an excimer laser (248 nm) at intensities of 10(7), 10(9), 10(10) and 10(11) W/m2 and doses up to 30 kJ/m2. The proportion of DNA as supercoil, open circular, linear and short fragments was determined by gel electrophoresis. Linear molecules were noted at fluences where supercoiled DNA was still present. The random occurrence of independent SSB in proximity to each other on opposite strands (producing linear DNA) implies introduction of numerous SSB per molecule in the sample. If so, supercoiled DNA that has sustained no SSB should not be observed. A model accounting for the amounts of supercoiled, open circular, linear and shorter fragments of DNA due to SSB, DSB and Scissions (opposition of two independently occurring SSB producing an apparent DSB) was developed, our experimental data and those of others were fit to the model, and quantum yields determined for SSB and DSB formation at each intensity. Results showed that high intensity laser radiation caused an increase in the quantum yields for both SSB and DSB formation. The mechanism of DSB formation is unknown, and may be due to simultaneous cleavage of both strands in one biphotonic event or the biased introduction of an SSB opposite a preexisting SSB, requiring two biphotonic events.

In tumor cell lines in which oncogene expression is abnormal, modulation of the expression of the oncogene (myc, src, or ras) by interferons (IFNs) has been observed concurrently with cell growth inhibition or phenotypic reversion. Oncogene expression has also been reported to vary during the differentiation of several neoplastic cell lines. Treatment of monolayer cultures of A43 1, a human epidermoid carcinoma cell line, with IFN-y resulted in rapid morphological alterations and cell death not seen with either IFN-a or IFN-/3. These changes were accompanied by elevated expression of mRNA's for p2 I (the c-ras gene product) and the epidermal growth factor receptor as well as increases in the biosynthetic rate of their respective proteins. These effects likewise appeared to be specific for IFN-y. Growth inhibition by IFN-y was also observed when A43 1 cells were grown in a three dimensional in vitro culture system. Immunohistochemical staining of these "tumoroids" with a differentiation specific, anti-keratin antibody indicated that IFN-y enhanced expression of this keratin. This observation suggests that the killing by IFN--y of A431 cells may result from an acceleraton of terminal differentiation. 0 1987 Society for Experimental Biology and Medicine. 319

<b><i>Introduction:</i></b> Deep brain stimulation (DBS) is commonly used in the treatment of medically refractory movement disorders. There have been several reports in the literature of edema developing around the implanted electrode. Most of these studies have been retrospective, suggesting that the time course and incidence of this edema are underestimated. An understanding of the incidence and time course of edema related to DBS leads is important to allow clinicians to better assess the correct course of action when edema following DBS implantation is observed. <b><i>Methods:</i></b> We examined both the time course and prevalence of edema following DBS implantation by obtaining a series of postoperative MRI scans from patients who underwent DBS surgery. Edema volume was quantified by a single neuroradiologist, measuring the peri-electrode T2 signal change. <b><i>Results:</i></b> We examined postoperative MRIs in thirteen patients with fifteen DBS electrode implants. Eleven patients exhibited white matter edema on at least 1 postoperative MRI, with none being symptomatic. Edema was completely resolved in 4 of the electrode implants through postoperative day 70, with the remaining cases still exhibiting edema at the last imaged time point. <b><i>Discussion/Conclusion:</i></b> In this study, we obtained a regimented series of postoperative MRIs in an effort to determine the time course and incidence of edema. Our results show that edema following DBS implant is not rare, is often asymptomatic, and may resolve over many weeks.