Photoactivation of 2-nitrofluorene in vitro and in the rat in vivo. UVA-induced formation of reactive intermediates that bind covalently to RNA and protein.
2-Nitrofluorene (2-NF), an environmental pollutant, can be activated by UV light to reactive intermediates that bind covalently to RNA and protein in vitro: high levels of covalent binding were obtained. This covalent binding was not dependent on the presence of oxygen in the solution and could be decreased by glutathione. Hydrolysis of the in vitro modified RNA and subsequent analysis of the liberated bases by HPLC revealed that approximately 15% of the covalent binding of 2-NF to RNA could be attributed to the formation of a guanosine adduct of nitroreduced 2-NF, N-(deoxyguanosin-8-yl)-2-aminofluorene. Many other adducts are formed of which the structure and mechanism of formation are as yet unknown. The possibility of photoactivation of 2-NF in the rat in vivo was also investigated. Photoactivation increased covalent binding of 2-NF in the skin but not in other organs. The mechanism of the photoactivation of 2-NF is discussed.
Wierckx
F C
FC
Division of Toxicology, University of Leiden, The Netherlands.
Beijersbergen van Henegouwen
G M
GM
van den Broeke
L T
LT
de Vries
H
H
Meerman
J H
JH
Mulder
G J
GJ
D000818:Animals; D001711:Biotransformation / Q000528:radiation effects; D005449:Fluorenes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D010777:Photochemistry; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014466:Ultraviolet Rays
D005449:Fluorenes; D011506:Proteins; C019499:2-nitrofluorene; D012313:RNA