Synthesis and photoirradiation of isomeric ethylchrysenes by UVA light leading to lipid peroxidation.
Polycyclic aromatic hydrocarbons (PAHs) are widespread genotoxic environmental pollutants. We have recently demonstrated that photoirradiation of PAHs leads to cytotoxicity, DNA damage, and induction of lipid peroxidation. In this paper we report the synthesis of all the six isomeric ethylchrysenes and the study of light-induced lipid peroxidation by these ethylchrysenes. 5-Ethylchrysene was synthesized by reaction of 5-keto-5,6,6a,7,8,9,10,10a-octahydrochrysene with CH3CH2MgBr followed by dehydration catalyzed by p-toluenesulfonic acid and dehydrogenation with DDQ in benzene. 1- and 4-Ethylchrysenes were similarly prepared by reaction of 1-keto-1,2,3,4,5,6-hexahydrochrysene and 4-keto-1,2,3,4-tetrahydrochrysenes, respectively with CH3CH2MgBr followed by dehydration and dehydrogenation. Direct acetylation of chrysene followed by Wolff-Kishner or Clemmensen reduction resulted in the formation of 2-, 3-, and 6-ethylchrysenes in 4%, 16%, and 43% yields, respectively. Photoirradiation of these compounds with 7 and 21 J/cm2 UVA light in the presence of methyl linoleate all resulted in lipid peroxidation. For comparison, photoirradiation of 4-methylchrysene and 5-methylchrysene was similarly conducted. For irradiation at a UVA light dose of 21 J/cm2, the level of induced lipid peroxidation is in the order 4-methylchrysene = 5-methylchrysene = 5-ethylchrysene = 4-ethylchrysene = chrysene > 1-ethylchrysene = 2-ethylchrysene > 3-ethylchrysene > 6-ethylchrysene. Compared with chrysene, these results indicate that the ethyl group at C4 or C5 position either slightly enhances or has no effect on the light-induced lipid peroxidation, while at C1-, C2-, C3-, or C6 position reduces light-induced lipid peroxidation.
Chen
Hui-Chan
HC
National Center for Toxicological Research, Jefferson, AR 72079, USA.
Xia
Qingsu
Q
Cherng
Shu-Hui
SH
Chen
Shoujun
S
Lai
Ching-Cheng
CC
Yu
Hongtao
H
Fu
Peter P
PP
D002911:Chrysenes / Q000633:toxicity*; D004249:DNA Damage; D006801:Humans; D015227:Lipid Peroxidation; D008054:Lipid Peroxides; D010789:Phototherapy; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D017382:Reactive Oxygen Species; D014466:Ultraviolet Rays / Q000009:adverse effects*
D002911:Chrysenes; D008054:Lipid Peroxides; D011084:Polycyclic Aromatic Hydrocarbons; D017382:Reactive Oxygen Species; C116651:ethylchrysene; C444840:hexahydrochrysene; C099739:octahydrochrysene; C031180:chrysene