Efficiency of DNA-histone crosslinking induced by saturated and unsaturated aldehydes in vitro.
Using a filter-binding assay based on precipitation of pUC13 plasmid DNA bound to calf-thymus histones, we have determined the efficiency of formation of DNA-protein crosslink formation induced by several aldehyde compounds in vitro. Formaldehyde, glutaraldehyde and acrolein were the most potent, causing 1 crosslink per 2.7 kbp of DNA at 1.5, 8 and 150 microM, respectively. All other compounds tested gave 1 crosslink per plasmid molecule in the mM concentration range as follows: acetaldehyde, 115 mM; propionaldehyde, 295 mM; butyraldehyde, 360 mM; crotonaldehyde, 8.5 mM; trans-2-pentenal, 6.3 mM. Significant decreases in the efficiency of DPXL formation were observed with monofunctional aldehydes of higher carbon chain length. For example, the concentration of formaldehyde needed to give 1 crosslink per molecule was almost 10(5) times less than that of acetaldehyde. Acetaldehyde differs from formaldehyde only by one saturated carbon. The presence of an unsaturated bond between the 2-3 carbons improved the potential for crosslink formation. For example, acrolein was over 500-fold more potent than propionaldehyde. Glutaraldehyde was almost as potent as formaldehyde, indicating that the bifunctional nature of this 5-carbon saturated aldehyde may be crucial to its high efficiency of DNA-protein crosslinking.
Kuykendall
J R
JR
Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours and Company, Newark, DE 19714.
Bogdanffy
M S
MS
D000171:Acrolein / Q000633:toxicity; D000447:Aldehydes / Q000633:toxicity*; D003432:Cross-Linking Reagents / Q000633:toxicity*; D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects* / Q000378:metabolism; D005557:Formaldehyde / Q000633:toxicity; D005976:Glutaral / Q000633:toxicity; D006657:Histones / Q000187:drug effects* / Q000378:metabolism; D009153:Mutagens; D016012:Poisson Distribution
D000447:Aldehydes; D003432:Cross-Linking Reagents; D004269:DNA, Bacterial; D006657:Histones; D009153:Mutagens; D005557:Formaldehyde; D000171:Acrolein; D005976:Glutaral