DNA-protein cross-links produced by various chemicals in cultured human lymphoma cells.
Chemicals such as cis-platinum, formaldehyde, chromate, copper, and certain arsenic compounds have been shown to produce DNA-protein cross-links in human in vitro cell systems at high doses, such as those in the cytotoxic range. Thus far there have only been a limited number of other chemicals evaluated for their ability to produce cross-links. The purpose of the work described here was to evaluate whether select industrial chemicals can form DNA-protein cross-links in human cells in vitro. We evaluated acetaldehyde, acrolein, diepoxybutane, paraformaldehyde, 2-furaldehyde, propionaldehyde, chloroacetaldehyde, sodium arsenite, and a deodorant tablet [Mega Blue; hazardous component listed as tris(hydroxymethyl)nitromethane]. Short- and long-term cytotoxicity was evaluated and used to select appropriate doses for in vitro testing. DNA-protein cross-linking was evaluated at no fewer than three doses and two cell lysate washing temperatures (45 and 65 degrees C) in Epstein-Barr virus (EBV) human Burkitt's lymphoma cells. The two washing temperatures were used to assess the heat stability of the DNA-protein cross-link, 2-Furaldehyde, acetaldehyde, and propionaldehyde produced statistically significant increases in DNA-protein cross-links at washing temperatures of 45 degrees C, but not 65 degrees C, and at or above concentrations of 5, 17.5, and 75 mM, respectively. Acrolein, diepoxybutane, paraformaldehyde, and Mega Blue produced statistically significant increases in DNA-protein cross-links washed at 45 and 65 degrees C at or above concentrations of 0.15 mM, 12.5 mM, 0.003%, and 0.1%, respectively. Sodium arsenite and chloroacetaldehyde did not produce significantly increased DNA-protein cross-links at either temperature nor at any dose tested. Excluding paraformaldehyde and 2-furaldehyde treatments, significant increases in DNA-protein cross-links were observed only at doses that resulted in complete cell death within 4 d following dosing. This work demonstrates that DNA-protein cross-links can be formed in vitro following exposure to a variety of industrial compounds and that most cross-links are formed at cytotoxic concentrations.
Costa
M
M
Institute of Environmental Medicine, New York University Medical Center, New York 10016, USA. costam@charlotte.med.nyu.edu
Zhitkovich
A
A
Harris
M
M
Paustenbach
D
D
Gargas
M
M
D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D000171:Acrolein / Q000378:metabolism / Q000633:toxicity; D000447:Aldehydes / Q000378:metabolism / Q000633:toxicity; D001149:Arsenates / Q000378:metabolism / Q000633:toxicity; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity; D005557:Formaldehyde / Q000378:metabolism / Q000633:toxicity; D005662:Furaldehyde / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D008697:Methane / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity; D009595:Nitroparaffins / Q000378:metabolism / Q000633:toxicity; D011108:Polymers / Q000378:metabolism / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000447:Aldehydes; D001149:Arsenates; D002273:Carcinogens; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D004852:Epoxy Compounds; D009153:Mutagens; D009595:Nitroparaffins; D011108:Polymers; D005557:Formaldehyde; C007366:diepoxybutane; D000171:Acrolein; C009277:sodium arsenate; D004247:DNA; C005556:propionaldehyde; C004656:chloroacetaldehyde; D005662:Furaldehyde; D000079:Acetaldehyde; D008697:Methane; C003043:paraform