Aliphatic/aromatic systems under irradiation: influence of the irradiation temperature and of the molecular organization.

With the aim of understanding the electronic excitation, charge or reactive species transfers occurring during irradiation, we studied the role of the aromatic content on ethylene/styrene random copolymers (PES) and on cyclohexane/benzene glasses (amorphous organic solids). Radiation-induced modifications were monitored in situ, at the molecular level, using Fourier transform infrared spectroscopy (FTIR). Irradiations were performed under a vacuum, and thanks to in situ measurements, oxidation was avoided. We followed both the C═C bond creation in the aliphatic moiety and the destruction of the aromatic moiety. The influence of the irradiation temperature was investigated by irradiating samples at room temperature and at 11 K. At such a low temperature, long-range migration hardly occurs and its influence is considerably reduced or could even vanish. Therefore, low temperature irradiation gives insight on the relative influence of reactive species transport and electronic excitation and charge transport. We found that the effect of lowering the PES irradiation temperature from room temperature to 11 K is small, indicating a minor role for the reactive species transport. Moreover, the two chosen systems allow the examination of the relative magnitude of intra- and intermolecular transfers. We demonstrate that, under conditions where reactive species are almost frozen, intermolecular transfers are very efficient.

Irradiation of ethylene/styrene copolymers: evidence of sensitization of the aromatic moiety as counterpart of the radiation protection effect.

Molecules containing aromatics systems are more stable in the presence of ionizing radiations than alkanes. In the same way, introducing aromatic rings into aliphatic compounds increases their stability. The protective effect is nonlocal and likely results from the transfer of energy and species from the aliphatic moiety to the aromatic one. For years, it was commonly assumed that the aromatic moiety, which is very radiation resistant, accommodates the extra energy remaining unaffected. The use of Fourier transform infrared spectroscopy, online with high energy ion beam irradiation of ethylene/styrene random copolymers, allows us to bring experimental evidence that the benzene rings are sensitized by transfer reactions and consequently that this effect is more important in polymers with low benzene ring molar content.

Hypoxanthine:guanine phosphoribosyltransferase activity in xenografts of human osteosarcoma.

It has recently been reported that human osteosarcomas may lack the purine salvage pathway enzyme, hypoxanthine:guanine phosphoribosyltransferase (EC 2.4.2.8). We have established a quantitative assay for measurement of this enzyme in human osteosarcoma xenografts with analysis of products by thin-layer chromatography. Nucleotidase or phosphatase activity was readily detected and could be abolished by preheating cytosol at 60 degrees C for 10 min and performing the assay at pH 10. Alternatively, the use of 25 mM NaF at pH 7.4 also inhibited this activity. The pH optimum for this enzyme in red blood cell sonicates and tumor cytosols was pH 10. All six human osteosarcoma xenografts contained hypoxanthine:guanine phosphoribosyltransferase activity ranging from 0.97 to 4.06 nmol/min/mg of protein at pH 7.4. Control human red blood cell sonicates demonstrated activity of 0.83 nmol/min/mg of protein. These data demonstrate that human osteosarcoma xenografts contain substantial activities of this purine salvage pathway enzyme.

Melphalan: a potential new agent in the treatment of childhood rhabdomyosarcoma.

Melphalan has been evaluated against a series of seven childhood rhabdomyosarcomas, each derived from a different patient and maintained in vivo as xenografts in immune-deprived mice. Six lines were derived from untreated tumors and one from a patient refractory to conventional therapy. At the maximum tolerated dose (LD10) a single administration of melphalan caused complete regressions of advanced tumor in six of seven lines, including xenografts derived from the refractory patient. This agent demonstrated activity over a broad range of doses, and was considerably more active than vincristine, cyclophosphamide, doxorubicin, and dactinomycin in the model.

Childhood rhabdomyosarcoma xenografts: responses to DNA-interacting agents and agents used in current clinical therapy.

A laboratory model of childhood rhabdomyosarcoma (RMS) has been used to evaluate cytotoxic agents used in current clinical protocols, and DNA-reacting agents that have had either limited or no evaluation in this histiotype. Seven lines of RMS each derived from a different patient were grown as xenografts in immune-deprived mice, six of these being from specimens derived from previously untreated patients. Of the 'conventional' agents, vincristine was the most effective. Of the other agents evaluated [L-phenylalanine mustard (L-PAM), cis-dichlorodiammineplatinum (cis-DDP), mitomycin C and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC)], L-PAM caused complete regressions in six of seven lines, including those resistant to cyclophosphamide. DTIC had marked activity in five tumors, and mitomycin C in three lines. Cyclophosphamide was active in five tumors, although efficacy was less marked in two lines in comparison to DTIC and mitomycin C.