The purpose of this study was to identify antimutagens in yogurt active against the
experimental colon carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Our
initial experiments showed that acetone extracts of yogurt, or milk fermented by various
lactic acid bacteria were antimutagenic against MNNG and 3,2'-dimethyl-4-aminobiphenyl
(DMAB) in the Ames test (Salmonella typhimurium TA 100). Further experiments carried
out with milk fermented by Lactobacillus delbrueckii ssp. bulgaricus 191R showed that
the putative compounds were more soluble in DMSO than in water, and that extractability
of activity against MNNG and DMAB varied with pH, suggesting the presence of
ionizable groups.
Subsequent experiments demonstrated the antimutagenicity of yogurt. An acetone
extract of yogurt was found to be active against a range of mutagens and promutagens in
the Ames test. Simulation of fermentation by addition of lactic acid, lactic acid bacteria, or
both to milk did not increase antimutagenicity, suggesting that compounds responsible for
the activity may be formed during fermentation. Conjugated linoleic acid (CLA), a known
dairy anticarcinogen, did not inhibit MNNG or DMAB indicating that other antimutagens
may be present in yogurt. Fractionation of the acetone extract by HPLC showed that anti-
MNNG and anti-DMAB activities did not co-elute, indicating that different compounds
were responsible for the two activities.
Using the Ames test to direct purification, isolation of an anti-MNNG active
compound was accomplished using silica gel, Sephadex LH-20 and C18 reversed phase medium pressure chromatographies. The antimutagen was identified as palmitic acid by:
a) co-elution with authentic palmitic acid on GC and HPLC columns, and b) by
comparison of mass and ¹³C-NMR spectra. Minor components of milk fat such as iso
methyl branched fatty acids (isopalmitic acid, isomargaric acid, isomyrsitic acid, and
isostearic acid) were found to be more active than their straight chain counterparts.
Isopalmitic acid also inhibited 4-nitroquinoline-N-oxide (4NQO) and the P450-mediated
activation of 7,12-dimethylbenz[a]anthracene (DMBA). The mechanism of
antimutagenesis against MNNG has not been established. / Graduation date: 1996
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/27052 |
| Date | 05 December 1995 |
| Creators | Sudarshan, Nadathur R. |
| Contributors | Bakalinsky, Alan Tagore |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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