PROTECTION OF CONJUGATED LINOLEIC ACIDS AGAINST 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE-INDUCED COLON CARCINOGENESIS IN THE F344 RAT - A STUDY OF INHIBITORY MECHANISMS

Citation
C. Liew et al., PROTECTION OF CONJUGATED LINOLEIC ACIDS AGAINST 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE-INDUCED COLON CARCINOGENESIS IN THE F344 RAT - A STUDY OF INHIBITORY MECHANISMS, Carcinogenesis, 16(12), 1995, pp. 3037-3043
Citations number
36
Categorie Soggetti
Oncology
Journal title
ISSN journal
01433334
Volume
16
Issue
12
Year of publication
1995
Pages
3037 - 3043
Database
ISI
SICI code
0143-3334(1995)16:12<3037:POCLAA>2.0.ZU;2-D
Abstract
Grilled ground beef contains a number of heterocyclic amine carcinogen s, such as 2-amino-3-methylimidazo[4,5f]quinoline (IQ), as well as ant icarcinogenic conjugated linoleic acids (CLA), In the present study, C LA was administered to male F344 rats by gavage on alternating days in weeks 1-4, while IQ was given by gavage every other day in weeks 3 an d 4 (100 mg/kg body wt), Rats were killed 6 h after the final carcinog en dose in order to quantify IQ-DNA adducts or after week 16 in order to CLA had no effect on the size of the foci, but inhibited significan tly (P < 0.05) the number of ACF/colon, from 4.3 +/- 2.4 in controls t o 1.1 +/- 1.3 in CLA-treated rats (mean +/- SD, n = 10). Rats given CL A also had significantly lower IQ-DNA adducts in the colon as determin ed by P-32-postlabeling analysis; relative adduct labeling levels (RAL x 10(7)) for the major adduct were 9.13 +/- 2.6 in controls versus 5. 42 +/- 1.8 in CLA-treated animals (P < 0.05), Mechanism studies indica ted that CLA and other fatty acids interact with certain heterocyclic amines in a manner consistent with substrate-ligand binding, However, no such interaction occurred with IQ, and CLA failed to inhibit signif icantly the mutagenicity of N-hydroxy-IQ in the Salmonella assay, Live r microsomes from CLA-treated rats exhibited lower activities for deal kylation of 7-ethoxyresorufin and methoxyresorufin and activated IQ to DNA binding species less effectively than microsomes from control ani mals, Direct addition of CLA to the in vitro incubation inhibited IQ-D NA binding and was associated with increased recovery of unmetabolized parent compound, In the Salmonella assay, CLA inhibited the mutagenic activity of IQ in the presence of so or ram seminal vesicle microsome s, Collectively, these results support a mechanism involving inhibitio n of carcinogen activation by CLA, as opposed to direct interaction wi th the procarcinogen, scavenging of electrophiles or selective inducti on of phase I detoxification pathways.