Genome-wide screening of indicator genes for assessing the potential carcinogenic risk of Nanjing city drinking water

Abstract

Effects of all pollutants existing in the Nanjing city drinking water (DWNC) on mouse gene transcription levels were measured to assess the DWNC carcinogenic risks and to identify candidate indicator genes for assessing and early warning the cancer risks. Transcriptional expression levels of 14,000 hepatic genes for the treatment group mice (Mus musculus, ICR) fed with DWNC for 90 days were detected using the GeneChip(®) Mouse Genome 430A 2.0 array. The analysis indicated that the transcriptional levels of 294 genes were up-regulated and 542 ones were down-regulated. Of these genes, 12 ones identified to be involved in at least five different types of cancers were further analyzed. An interrogation by Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that three (including ITGAV, CCND1 and SMAD2) of the 12 genes were mapped to pathway in cancer. Gene Ontology (GO) function annotation also showed that they were associated with the functional categories of cell cycle regulation, adhesion, apoptosis, signal transduction and so on which are closely implicated in tumorigenesis and progression. The correlations between the aberrant expressions of them and the genesis and progression of cancers have been further documented by a number of scientific researches. These results might demonstrate that the potential toxicity and carcinogenic risks were associated with DWNC. Moreover, ITGAV, CCND1 and SMAD2 were identified as the most likely candidate indicator genes for the assessment of the combined carcinogenic risk of all pollutants existing in DWNC.

A transcriptomics study on hepatic lipid metabolism in mice exposed to contaminated drinking water

“…7.543 ± 0.095 2.537 ± 0.068 N. (Sun et al 2011;Zhang et al 2011a;Chen et al 2012). During the animal exposure, average water intake of each mouse was 5.75 ± 0.17 g d -1 in NJS group, 5.17 ± 0.40 g d -1 in NJT group and 5.86 ± 0.34 g d -1 in control group.…”

“…Previous studies also showed that feeding mice with Taihu Lake (China) water posed no significant effect on water intake and body weight (Zhang et al 2011b;Qin et al 2012). Although the trace-level pollutants in Yangtze River water cannot obviously affect mice survival and growth, it has been indicated that exposure to the water may disturb hepatic mRNA expression of many genes involved in carcinogenesis (Zhang et al 2011a;Sun et al 2011) and reproductive toxicity ).…”

“…This hypothesis is supported by a metabolomics study suggesting that the drinking water from Yangtze River can induce liver dysfunction characterized by disorder of branched-chain amino acid and energy metabolism, as well as perturbation of glucose-alanine cycle (Zhang et al 2011c). Moreover, expression of hepatic mRNA involved in cancer genesis and development was also found to be altered in the mice fed with the river water (Zhang et al 2011a;Sun et al 2011). …”

Proteomics Approach (iTRAQ) to Test Subchronic and Chronic Toxicity Effects of Mice Exposed to Drinking Water Source from Yangtze River Delta

“…The Yangtze River is the main source of drinking water for cities located in southeast of China. Many pollutants at low concentrations have been found in this river, such as organochlorine pesticides (OCPs), phthalates (PAEs), polycyclic aromatic hydrocarbons (PAHs), and heavy metals (especially cadmium and arsenic) [3][4][5][6]. Not all these possible carcinogens are efficiently removed during the process of treatment of drinking water sources.…”

“…And this conclusion had also been proved by other tests. Long-term exposure to drinking water source from Yangtze River Delta may lead to DNA damage and oncogenesis disorders in mouse models [3][4][5][6].…”