MODULATION OF 8-METHOXYPSORALEN-DNA PHOTOADDUCT FORMATION BY CELL DIFFERENTIATION, MITOGENIC STIMULATION AND PHORBOL ESTER EXPOSURE IN MURINE T LYMPHOCYTES

Abstract The effects of cell differentiation and mitogen and phorbol ester stimulation on the formation of 8-methoxypsoralen (8-MOP)-DNA photoadducts in murine T lymphocytes were examined using ³H-8-MOP. While there were no significant differences in 8-MOP photoadduct formation among BALB/c thymocytes, splenocytes, splenic T cells and MRL/1pr lymph node cells, BALB/c bone marrow cells showed fewer photoadducts than did the lymphocytes. This suggested that proliferating progenitor cells may be resistant to 8-MOP photoadduct formation. Incubation of purified splenic T cells with lectin mitogens for 2 h or with phorbol 12-myristate 13-acetate (PMA) for 2–43 h resulted in reduction of 8-MOP photoadduct formation in the DNA, whereas 64 h cultivation with these agents augmented the photoadduct formation. The reduction of photoadduct formation induced by phytohemagglutinin was restored by the further addition of a protein kinase C (PKC) inhibitor, H-7, to the culture. Thus, it is assumed that the reduction of adduct formation evoked by mitogens and PMA is mediated in part by the activation of PKC in the cells. On the other hand, the augmentation of the adduct formation induced by the longer-period cultures with mitogens and PMA appeared to be caused by down-regulation of PKC. The present study showed that the stimulatory signals in which PKC is presumably involved affect the ability of cells to form 8-MOP-DNA photoadducts.     

A computational analysis of the alkane pyrolysis mechanism: Sensitivity analysis of individual reaction steps

The previously reported extensive mechanism for the pyrolysis of propane and n-butane around 800 K is reexamined in the light of a recent reevaluation of the rate constant data base, and the sensitivity of model simulations to variations in the rate parameters is studied. The pyrolysis rates of butane and the product distribution of propane remain in good agreement with the available experiments, while the rate of propane and the product distribution of butane now show significant differences. The linear sensitivity analysis of the reaction matrix demonstrates an intimate coupling between initiation, hydrogen abstraction, radical decomposition, and recombination reactions as primarily responsible for the overall behavior of the mechanism. The role of unsaturated radicals in the self-inhibition of the pyrolysis process is quantitatively established. The study of the sensitivity coefficients for butane product formation has permitted pinpointing those specific reaction steps in the mechanism which are most likely responsible for the remaining discrepancies between model and experiment. This particular example demonstrates the usefulness of sensitivity calculations for the isolation of reactions for which improvements in rate parameter values are needed.     

Improved generation of anti-tumor immunity by antigen dose limitation

Background  

The malignant cells of cutaneous T cell lymphoma (CTCL) display immunogenic peptides derived from the clonal T cell receptor (TCR) providing an attractive model for refinement of anti-tumor immunization methodology. To produce a clinically meaningful anti-tumor response, induction of cytotoxic anti-CTCL cells must be maximized while suppressive T regulatory cells (Treg) should be minimized. We have demonstrated that engulfment of apoptotic CTCL cells by dendritic cells (DC) can lead to either CD8 anti-CTCL responses or immunosuppressive Treg induction. Treg generation is favored when the number of apoptotic cells available for ingestion is high.     

Molar extinction coefficients of some carbohydrates in aqueous solutions

Molar extinction coefficients of some carbohydrates viz. l-arabinose (C₅H₁₀O₅), d-glucose (C₆H₁₂O₆), d-mannose (C₆H₁₂O₆), d-galactose (C₆H₁₂O₆), d(-) fructose (C₆H₁₂O₆) and maltose (C₁₂H₂₄O₁₂) in aqueous solutions have been determined at 81, 356, 511, 662, 1173 and 1332 keV by gamma ray transmission method in a narrow beam good geometry set-up. These coefficients have been found to depend upon the photon energy following a 4-parameter polynomial. These extinction coefficients for different sugars having the same molecular formula have same values varying within experimental uncertainty. Within concentration ranges studied, Beer-Lambert law is obeyed very well.     

Fourth order nonselfadjoint differential equations with clamped-free boundary conditions

Summary A class of nonselfadjoint fourth order differential equations is investigated in this paper by a pair of equations of the second order. Special attention is given to establishing conditions for the existence of solutions subject to two point boundary conditions, and is achieved basically through various characterizations, comparison theorems and related eigenvalue problems. Entrata in Redazione il 1^o giugno 1977. The first author is supported by the NRC of Canada under Grant number A3105.     

Computational modeling of the mechanisms of the free radical-chain reaction of alkanes with oxygen. The oxidation of isobutane,n-butane,and isopentane

A general computational method for obtaining complete solutions of time-dependent kinetic equations has been developed and applied to free radical-initiated reactions of alkanes with oxygen. The method has been applied to the low-temperature, peroxide-initiated oxidations of isobutane and isopentane. Using available independently measured and estimated values for the rate constants and activation parameters for each of the 20 proposed reaction steps for the oxidation of isobutane, the rates and products have been calculated for both the liquid phase and gas phase in the range of 100°–155°C. The calculated rates and products of oxidation agree with published experimental values. The oxidation of isopentane was examined by a 32-reaction model. The rate constants were estimated using values for the appropriate rate steps in the oxidation of n-butane and isobutane. The calculation of the oxidation rate and products agree with our experiments.     

The two-photon excitation spectrum of fluorene near 6 K

The two-photon fluorescence excitation spectrum of the fluorene single crystal at about 6 K is reported. Two k = 0 exciton bands arising from the p     

HPLC ANALYSIS OF 4'',5''-MONOADDUCT FORMATION IN CALF THYMUS DNA and SYNTHETIC POLYNUCLEOTIDES TREATED WITH UVA and 8-METHOXYPSORALEN

Abstract— 8-methoxypsoralen monoadduct formation in calf thymus DNA irradiated with subbands of ultraviolet A light has been quantitated by HPLC analysis of the enzymatic hydrolysates of the DNA. Normalization of the yield of monoadducts for the variation in source output and the absorptivity of 8-MOP at each of the irradiating wavelengths showed that the 4',5'-furan monoadduct was the principal photoproduct and the efficiency of its formation was independent of irradiating wavelength. Synthetic polynucleotides irradiated with ultraviolet A light demonstrated a base composition and sequence dependence for 8-MOP photoreactivity: (poly(dAdT.dAdT) > poly(dA.dT) > poly(dGdC.dGdC) in both the B and Z forms > pofy(dT).