DNA modification in vivo by derivatives of glucose: enhancement by glutathione depletion.
When BHK or HTC cells are cultured for 20 min with [U-14C]glucose in the presence of agents that deplete reduced glutathione, DNA banded from the cells in cesium salt gradients containing guanidium HCl is radioactively labeled. This depletion-dependent labeling required live cells. It was not caused by reactive contaminants in the radioactive glucose preparations, by carbohydrate or protein comigration into the DNA band, or by metabolism of glucose into deoxyribose. Labeling levels are similar whether depletion is achieved by oxidation (with the drug diamide) or by inhibition of synthesis (with methionine sulfoximine). A temporal association between GSH repletion and the appearance of D-lactate, the putative unique product of GSH-dependent glyoxylase action on pyruvaldehyde, suggests possible involvement of 3-carbon dicarbonyls.
Shires
T K
TK
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Tresnak
J
J
Kaminsky
M
M
Herzog
S L
SL
Truc-Pham
B
B
D002460:Cell Line; D002500:Centrifugation, Isopycnic; D004247:DNA / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000494:pharmacology; D011765:Pyruvaldehyde / Q000378:metabolism
D007773:Lactates; D008717:Methionine Sulfoximine; D019344:Lactic Acid; D011765:Pyruvaldehyde; D006003:Glycogen; D004247:DNA; D007791:Lactoylglutathione Lyase; D005978:Glutathione; D005947:Glucose