Naturally occurring chlorophyll derivatives inhibit aflatoxin B1-DNA adduct formation in hepatoma cells.
The inhibitory effects of four chlorophyll derivatives (chlorophyllide [Chlide] a and b and pheophorbide [Pho] a and b) on aflatoxin B1 (AFB1)-DNA adduct formation, and on the modulation of hepatic glutathione S-transferase (GST) were evaluated in murine hepatoma (Hepa-1) cells. Enzyme-linked immunosorbent assay showed that pretreatment with Chlide or Pho significantly reduced the formation of AFB1-DNA adducts, and that Pho was the most potent inhibitor. However, wash-out prior to adding AFB1 totally eliminated inhibition by Childe and partially eliminated inhibition by Pho, indicating that the inhibitory effect of Chlide, and to some extent Pho, was mediated through direct trapping of AFB1. Furthermore, spectrophotometric analysis showed that Pho treatment could increase GST activity in Hepa-1 cells. These observations indicate that the chlorophyll derivatives studied may attenuate AFB1-induced DNA damage in the Hepa-1 cell by direct trapping of AFB1. Pho provided additional protection not only by direct trapping, but also by increasing GST activity against hepatic AFB1 metabolites.
Hsu
Ching-Yun
CY
College of Pharmacy, School of Nutrition and Health Science, Taipei Medical University, Taipei 110, Taiwan.
Chen
Yue-Hwa
YH
Chao
Pi-Yu
PY
Chen
Chiao-Ming
CM
Hsieh
Ling-Ling
LL
Hu
Shene-Pin
SP
D016604:Aflatoxin B1 / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002735:Chlorophyllides / Q000494:pharmacology; D018736:DNA Adducts / Q000378:metabolism* / Q000633:toxicity; D005982:Glutathione Transferase / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice
D016588:Anticarcinogenic Agents; D002735:Chlorophyllides; D018736:DNA Adducts; C072611:aflatoxin B1-DNA adduct; D002734:Chlorophyll; C046016:chlorophyllide b; C034388:chlorophyllide a; C032624:pheophorbide b; D016604:Aflatoxin B1; D005982:Glutathione Transferase; C032623:pheophorbide a