TY - JOUR
T1 - Identification and characterization of chlorin e4 ethyl ester in sera of individuals participating in the chlorophyllin chemoprevention trial
AU - Egner, P. A.
AU - Stansbury, K. H.
AU - Snyder, E. P.
AU - Rogers, M. E.
AU - Hintz, P. A.
AU - Kensler, T. W.
PY - 2000
Y1 - 2000
N2 - Chlorophyllin (CHL), a mixture of water soluble derivatives of chlorophyll, has been shown to be an effective inhibitor of aflatoxin B1 (AFB1) carcinogenesis and AFB1-DNA adduct formation 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 previously attributed to molecular complexing. In 1997, a randomized, double-blind clinical trial of CHL was conducted in Qidong, Jiangsu Province, People's Republic of China. At the completion of the study, when serum samples were regrouped by subject identification number, it was noted that many of the participant samples were green in color. Using HPLC, ESI/MS, and MS/MS techniques, serum samples from individuals receiving CHL were found to contain previously unreported 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 and bioavailability of two chlorin derivatives suggests that the mechanism of CHL chemoprevention may lie in the actions of these two components in vivo in addition to preventing carcinogen absorption from the gut.
AB - Chlorophyllin (CHL), a mixture of water soluble derivatives of chlorophyll, has been shown to be an effective inhibitor of aflatoxin B1 (AFB1) carcinogenesis and AFB1-DNA adduct formation 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 previously attributed to molecular complexing. In 1997, a randomized, double-blind clinical trial of CHL was conducted in Qidong, Jiangsu Province, People's Republic of China. At the completion of the study, when serum samples were regrouped by subject identification number, it was noted that many of the participant samples were green in color. Using HPLC, ESI/MS, and MS/MS techniques, serum samples from individuals receiving CHL were found to contain previously unreported 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 and bioavailability of two chlorin derivatives suggests that the mechanism of CHL chemoprevention may lie in the actions of these two components in vivo in addition to preventing carcinogen absorption from the gut.
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U2 - 10.1021/tx000069k
DO - 10.1021/tx000069k
M3 - Article
C2 - 10995263
AN - SCOPUS:0033805542
SN - 0893-228X
VL - 13
SP - 900
EP - 906
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 9
ER -