The antimutagenic potency of wheat grain and berry extracts was studied in
vitro against several heterocyclic amines (HCAs) using the Salmonella
mutagenicity assay and the anticarcinogencity of wheat grain was studied in vivo
using the rat colonic aberrant crypt focus assay.
Wheat bran, which binds HCAs in vitro, as well as refined wheat and
unrefined whole wheat, inhibited the mutagenic activities of 2-amino-3-
methylimidazo [4, 5-f] quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)
when they were co-incubated and the supernatant (minus grain) was added to the
Salmonella mutagenicity assay. The water-soluble fraction alone from refined and
unrefined wheat, but not bran, also inhibited these mutagens in vitro. In vivo, AIN-
93G diets containing refined wheat or unrefined wheat were examined for their
ability to inhibit IQ-induced colonic aberrant crypt foci (ACF) in the F344 rat. A
slight increase in the number of aberrant crypts/ACF (AC/ACF) was seen after 16
weeks in rats treated post-initiation with refined wheat (p<0.05), and fewer foci
with 2 or 3 aberrant crypts (ACF-2) were found in rats given unrefined whole
wheat post-initiation compared with animals treated with the same diet during the
initiation phase (p<0.05). There was no significant difference in the profile of IQ
urinary metabolites or excretion of promutagens 0-48 hours after carcinogen
dosing, and grains had no effect on hepatic cytochrome P450 (CYP) 1A1,
CYP1A2, aryl sulfotransferase, or N-acetyltransferase activities; however, a
slightly higher UDP-glucuronosyl transferase activity was observed in rats fed
unrefined wheat compared with refined wheat diets (p<0.05). Thus, despite their
antimutagenic activities in vitro, only marginal effects were seen with refined and
unrefined wheat in vivo with respect to induction of hepatic enzyme activities,
carcinogen metabolism, or IQ-induced ACF in the rat colon.
The fresh juice and extract of crandall black currant (Ribes aureum) were
not mutagens in the Salmonella mutagenicity assay. Berry extract or fresh juice at
levels to 50 ��l (22 mg berry) in a 500 ��l pre-incubation system significantly
inhibited the mutagenicity of IQ, a mutagen from cooked meat, by 32% when rat
liver S9 bioactivation system was present. One hundred ��l of crandall black currant
extract gave 89% inhibition of IQ mutagenicity (p<0.05). However, the
mutagenicity of 2-hydroxyamino-3-methylimidazo[4,5-f] quinoline (N-hydroxy-
IQ), a direct-acting metabolite of IQ, was not affected. An in vitro fluorometric
assay showed the activity of cytochrome P 450 (CYP) 1A1 and CYP 1A2 was
decreased. Inhibition of CYP 1A2 activity may be an important mechanism of
antimutagenicity of crandall black currant extract. Similar results were also
observed with other berry samples.
Key word: cereal grains, black currant, berry, aberrant crypt foci, heterocyclic
amines, CYP1A1, CYP1A2, Salmonella mutagenicity assay. / Graduation date: 2003
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/32134 |
| Date | 15 October 2002 |
| Creators | Yu, Zhen |
| Contributors | Williams, David E. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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