Identification and Characterization of Chlorin e4 Ethyl Ester in Sera of Individuals Participating in the Chlorophyllin Chemoprevention Trial

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• 作者：Patricia A. Egner ; Kevin H. Stansbury ; Edward P. Snyder ; Mark E. Rogers ; Paul A. Hintz ; and Thomas W. Kensler
• 刊名：Chemical Research in Toxicology
• 出版年：2000
• 出版时间：September 2000
• 年：2000
• 卷：13
• 期：9
• 页码：900 - 906
• 全文大小：104K
• 年卷期：v.13,no.9(September 2000)
• ISSN：1520-5010

文摘

Chlorophyllin (CHL), a mixture of water soluble derivatives of chlorophyll, has been shownto be an effective inhibitor of aflatoxin B₁ (AFB₁) carcinogenesis and AFB₁-DNA adductformation in rainbow trout and rats [Breinholt, V., Hendricks, J., Pereira, C., Arbogast, D.,and Bailey, G. (1995) Cancer Res. 55, 57-62; Kensler, T. W., Groopman, J. D., and Roebuck,B. D. (1998) Mutat. Res. 402, 165-172]. The chemopreventive action of CHL has been previouslyattributed to molecular complexing. In 1997, a randomized, double-blind clinical trial of CHLwas conducted in Qidong, Jiangsu Province, People's Republic of China. At the completion ofthe study, when serum samples were regrouped by subject identification number, it was notedthat many of the participant samples were green in color. Using HPLC, ESI/MS, and MS/MStechniques, serum samples from individuals receiving CHL were found to contain previouslyunreported copper chlorin e₄ ethyl ester (CuCle₄ ethyl ester) as well as copper chlorin e₄(CuCle₄). Both chlorins originated in the study tablet, were absorbed into the bloodstream,and conferred a green color to the sera. This initial finding of in vivo absorption andbioavailability of two chlorin derivatives suggests that the mechanism of CHL chemopreventionmay lie in the actions of these two components in vivo in addition to preventing carcinogenabsorption from the gut.