4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Circulating MicroRNA Deregulation in Early Lung Carcinogenesis

Objective To study the alteration of circulating microRNAs in 4-（methylnitrosamino）-l-（3-pyridyl） -l-butanone （NNK）-induced early stage lung carcinogenesis. Methods A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 2, 5, 20, and 20 following NNK treatment. Results No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment. Conclusion The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.

The Correlation between the Intrinsic and Extrinsic Molecular Markers in the Inhibition of the Lungs Carcinogenesis Growth by Mahkota Dewa Polyphenols on Balb/c Mouse

Phytochemical analysis shows that mahkota dewa fruit contains polyphenols. Mahkota dewa polyphenols have the ability to disrupt or reverse the stages of cancer or a carcinogenesis process by affecting the intracellular signaling tissue molecules involved in an initiation and/or promotion. This chemopreventive potential is highly anticipating. The use, effectiveness, and benefits of the polyphenol have been empirically and pre-clinically proved without side effects. A multivariate analysis using Spearman’s test was conducted to examine the correlation between variables. Meanwhile, to determine which dependent variables played the strong role, a discriminant function analysis was performed with a significance level of p < 0.05 and a reliability level of 95%. The results showed that the mahkota dewa polyphenols acted as the suppressor agent by inducing apoptosis. This finding proved that polyphenols addition might result in death signal transduction through an apoptosis pathway which is either mediated by death receptor or mitochondria. The results of this study indicate that there is a relationship between apoptotic cell death mediated by death receptor and mitochondria through the administration of mahkota dewa polyphenols, it can be argued that mahkota dewa polyphenols can function in lung cancer chemoprevention in mice strain Balb/c.

GST-π EXPRESSION IN TRANSFORMED CELLS BY TRANSFECTING OF DNA ISOLATED FROM HUMAN FETAL LUNG TISSUES TREATED WITH CARCINOGENS

This work was supported by a grant from National Education Committee of China.Abbreviations: GST, glutathione Stransferase; GSTπ, GST pi class; DEN, diethylnitrosamine; MNU, Nmethylnitrosourea; CSC, cigarette smoke condensate; HFL, human fetal lung; CDNB, 1chloro2,4dinitrobenzene. Objective : To investigate the relationship between the GSTs, GSTπ expression and initiation of lung carcinogenesis. Methods: The Rat1 cells were transformed by carcinogens (DEN, MNU and CSC) treated fetal lung DNA for 24 h. Results: The GSTs activities toward 1chloro2, 4dinitrobenzene (CDNB) in transformed cells were significantly higher than in the solvent control cells (P<005). GSTπ content and GSTπ mRNA expression level of transformed cells were also higher than those of control cells which were performed by ELISA and Northern blotting method respectively. The results indicated that the higher GSTS activities of transformed cells were due to the increase of GSTπ content and the GSTπ mRNA overexpressing may be responsible for the increase of GSTπ protein level of the transformed cells. Conclusion: The changes of GSTs and GSTπ may be considered as the one of the biomarkers of the initiation of human lung carcinogenesis.