Inhibition of conjugated linoleic acid on mouse forestomach neoplasia induced by benzo (a) pyrene and chemopreventive mechanisms.
OBJECTIVE
To explore the inhibition of conjugated linoleic acid isomers in different purity (75 % purity c9,t11-, 98 % purity c9,t11- and 98 % purity t10,c12-CLA) on the formation of forestomach neoplasm and chemopreventive mechanisms.


METHODS
Forestomach neoplasm model induced by B(a)P in KunMing mice was established. The numbers of tumor and diameter of each tumor in forestomach were counted; the mice plasma malondialdehyde (MDA) were measured by TBARS assay; TUNEL assay was used to analyze the apoptosis in forestomach neoplasia and the expression of MEK-1, ERK-1, MKP-1 protein in forestomach neoplasm were studied by Western Blotting assay.


RESULTS
The incidence of neoplasm in B(a)P group, 75 % purity c9, t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10, c12-CLA group was 100 %, 75.0 %(P>0.05), 69.2 % (P<0.05) and 53.8 % (P<0.05) respectively and the effect of two CLA isomers in 98 % purity on forestomach neoplasia was significant; CLA showed no influence on the average tumor numbers in tumor-bearing mouse, but significantly decreased the tumor size, the tumor average diameter of mice in 75 % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10, c12-CLA group was 0.157+/-0.047 cm, 0.127+/-0.038 cm and 0.128+/-0.077 cm (P<0.05) and 0.216+/-0.088 cm in B(a)P group; CLA could also significantly increase the apoptosis cell numbers by 144.00+/-20.31, 153.75+/-23.25, 157.25+/-15.95(P<0.05) in 75 % purity c9,t11-CLA group, 98 % purity c9,t11-CLA group and 98 % purity t10,c12-CLA group (30.88+/-3.72 in BP group); but there were no significant differences between the effects of 75 % purity c9,t11-CLA and two isomers in 98 % purity on tumor size and apoptotic cell numbers; the plasma levels of MDA in were increased by 75 % purity c9,t11-CLA, 98 % purity c9,t11-CLA and 98 % purity t10,c12-CLA. The 75 % purity c9,t11-CLA showed stronger inhibition; CLA could also inhibit the expression of ERK-1 protein and promote the expression of MKP-1 protein, however no influence of CLA on MEK-1 protein was observed.


CONCLUSIONS
Two isomers in 98 % purity show stronger inhibition on carcinogenesis. However, the inhibitory mechanisms of CLA on carcinogenesis is complicated, which may be due to the increased mice plasma MDA, the inducing apoptosis in tumor tissues. And the effect of CLA on the expression of ERK-1 and MKP-1 may be one of the mechanisms of the inhibition of CLA on the tumor.
Chen
Bing-Qing
BQ
Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin 150001, Heilongjiang Province, China. bingqingchen@sina.com
Xue
Ying-Ben
YB
Liu
Jia-Ren
JR
Yang
Yan-Mei
YM
Zheng
Yu-Mei
YM
Wang
Xuan-Lin
XL
Liu
Rui-Hai
RH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D018797:Cell Cycle Proteins; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D054638:Dual Specificity Phosphatase 1; D017874:Immediate-Early Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D019787:Linoleic Acid / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation; D048369:MAP Kinase Kinase 1; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011897:Random Allocation; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D018797:Cell Cycle Proteins; D004042:Dietary Fats, Unsaturated; D017874:Immediate-Early Proteins; D017392:Thiobarbituric Acid Reactive Substances; D001564:Benzo(a)pyrene; D019787:Linoleic Acid; D017346:Protein Serine-Threonine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases