Carcinogenesis, Vol 19, 1323-1326, Copyright © 1998 by Oxford University Press
U Harttig and GS Bailey
Naturally occurring chlorophylls (Chl) have shown anti-mutagenic activity
but little is known about their chemoprotective properties in vivo. This
study examined the effect of Chl on formation in vivo of DNA adducts by the
potent environmental carcinogen dibenzo[a,l]pyrene (DBP), using rainbow
trout as the animal model. Fingerling trout were fed diets containing 200
p.p.m. DBP alone or with one of the following preparations incorporated at
3000 p.p.m. total chlorins: purified pheophytin a (Phe a) (94%);
semi-purified Chl a (77%, 23% Phe a), commercial Chl a (88%, 12% other Chl
a-related compounds); crude spinach extract (53% Chl a, 19% Chl b, 14% Phe
a, 9% carotenoids); commercial Cu-chlorophyllin (55% chlorins, 45% neutral
salts), as a known inhibitory control. After 2 weeks dietary treatment, the
animals were killed and organs were collected. Stable DBP-DNA adducts from
liver were quantified after 33P-post-labeling and separation by
reversed-phase HPLC. Total DBP-DNA adducts in the DBP-only group were 2.46
+/- 0.32 adducts/10(6) nucleotides. All chlorophyll treatment groups showed
significantly lower adduct levels (P < 0.001, Tukey's HSD test), as
follows: crude spinach extract, 0.64 +/- 0.14; semi-pure Chl a, 0.5 +/-
0.11; commercial Chl a, 1.26 +/- 0.17; Phe a, 0.95 +/- 0.01; chlorophyllin,
0.78 +/- 0.09. The various treatments suppressed DBP-DNA adducts
essentially uniformly across the HPLC profile, which is consistent with
complex formation and reduced carcinogen uptake as the predominant
protective mechanism. The chlorophyll-mediated reduction in DBP-DNA adducts
in vivo is the first demonstration of anti-genotoxic activity of these
common dietary phytochemicals in any vertebrate animal model.
ARTICLES
Chemoprotection by natural chlorophylls in vivo: inhibition of dibenzo[a,l]pyrene-DNA adducts in rainbow trout liver
Department of Environmental and Molecular Toxicology, and Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis 97331, USA. harttigu@bcc.orst.edu
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