Karl A. Schellenberg

Polyethylene glycol as a protector against head and neck irradiation

Mice injected i.p. with polyethylene glycols (PEG) 20 min prior to head and neck X irradiation with 1650 rad showed improved survival, increased food and water consumption, and retention of body weight compared with irradiated controls. The LD 50/15 for PEG-treated mice was 1900 +/- 108 rad compared to 1527 +/- 56 for the controls. PEG of molecular weights 200, 400, and 600 afforded significant levels of radioprotection; PEG of molecular weights 1000, 1450, 4000, and 20,000 when given at maximum tolerated doses (approximately 0.5 LD 50) did not. The degree of radioprotection by PEG with molecular 400 given 20 min before irradiation increased with dose up to the maximum tolerated dose of 6.4 g/Kg. Significant, but lower, levels of radioprotection were observed when the PEG was given 5 min after irradiation. Mice injected i.p. with PEG, cystamine, 5-thioglucose, chlorpromazine, polyethylene glycol monomethyl ether or polyvinylpyrrolidone all had comparable survival levels. Polypropylene glycol, polyethylene glycol diacrylate, and polycaprolactonediol were more toxic than PEG and showed no radioprotection.

The reaction of protein tryptophanyl residues with reduced nicotinamide adenine dinucleotide: Structure of a model adduct

Abstract The 3H labeling of yeast alcohol dehydrogenase, following treatment with [4-3H]NADH and acid hydrolysis, has been reexamined. Although earlier evidence suggested that the label was in a tryptophanyl residue, the present study has shown that the labeling is due, at least in part, to an acid-catalyzed addition of the dihydronicotinamide moiety to a tryptophanyl residue of the protein. The same adduct appeared to be formed from the reaction of NADH with N-acetyltryptophan in place of enzyme. The analogous adduct from the model compounds 1-(2-dimethylaminoethyl)-1,4-dihydronicotinamide and 3-methylindole had the structure 1-(dimethylaminoethyl)-6-(3-methyl-3H-indol-3-yl)-1,4,5,6-tetrahydronicotinamide. These results indicate that the labeling was due to an electrophilic attack by the 6 position of the dihydropyridine on the 3 position of the indole.