| Formaldehyde is one of the most important contamination in ourenvironment. It is well-known of its toxicity to body especially therespiration system. "Twenty-six scientists from 10 countries evaluated theavailable evidence on the carcinogenicity of formaldehyde, a widely usedchemical, and concluded formaldehyde is carcinogenic to humans ",reported in Press Release. NO. 153 in June 2004, by the InternationalAgency for Research on Cancer (IARC). The current opinion about thepossible carciongenic mechanisms of formaldehyde are following: 1)protein-DNA crosslinking, DNA oxidation damage or gene mutation, 2)genetic toxicity such as chromosome aberrance, sister chromatidexchanges,and so on, 3) promoting the proliferation of cells. The directevidence for the carcinogenesis of these formaldehyde toxicity is stilllacking, and some phenomenons in the experimental animals can not beexplained by the above machanisms. One of such examples was observedby Monticello TM, who has found there is no direct correlation betweensites susceptible to formaldehyde-induced nasal cancer and sites ofcellular injury in Fischer-344 rats exposed to formaldehyde. Theseresults indicated that the carcinogenesis of formaldehyde may not due to direct chemical damage, but other machanism.The recent progress in cancer stem cells (CSCs) maybe help us toexplain the above observation. Cancer stem cells (CSCs) are capable ofinitiating and sustaining growth of the tumor, with the feature ofself-renewal. Self-renewal is a unique cell division in which the capacityof one or both progeny to proliferate and differentiate is similar to thoseof the parental cell, and realize the self-copy. The capacity of serf renewalallows the mutation in stem cells pass to the next generation, on the otherhand, the single mutant stem cell can form the differentiated cellscontained in tumor tissues because of its pluripotent potential. The lastreports suggested loss of control over self-renewal decisions maybe themost important reason for the caricinogenesis of CSCs. The discovery ofCSCs extends greatly our understanding of carcinogenesis, and supply usnew visual angle for clinic tumor research and therapy.Based on the above background, we have proposed the followinghypothesis: formaldehyde can make the loss of control over self-renewaldecisions of CSCs, and stimulate the transformation of CSCs to tumorcells. By such carcinogenesis mechanism, it is not necessary that the sitesof tumor formation are the same of cellular injury in theformaldehyde-induced animal model.In our project, P19 cell line was selected as cell model. P19 cell line was a kind of embryonal carcinoma and derived from mouseteratocarcinoma, and was very similar with CSCs in many aspectsincluding the features of pluripotent potential and self-renewal. Firstly,we treated P19 cells with formaldehyde, and analydsis the changes incellular phenotype by observing the celluar morphological feature.Secondly, the gene expression patterns of normal cells andmorphologically changed cells were high-throughout detected by cDNAmicroarray analysis, those genes that their expression levels werechanged more than 2 folds between control cells andformaldehyde-treated cells were selected for further analysis, and thechanged levels of those genes were confirmed by quantitative real-timereverse-transcription PCR. Using bioinformatic techeniques, the changedgenes after formaldehyde treatment were classed according theirbiological function, and those genes involved in cell self-renewalregulation were selected for further gene regulation pathway analysis,which will provide theoretic evidences for the regulation of formaldehydein cell self-renewal.
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