The Effects Of Chronic Ethanol Exposure On The Cytotoxicity And Genetoxicity Of Human Colorectal Adenocarcinoma Cells And Normal Colon Epithelial Cells

Wine is a beverage in daily life, its main ingredient is Ethanol,and wine culture isvery important in art、diet、cooking and health-care,but it is clearly a toxic substanceto the human body, when consumed in excess,it is associated with with increased riskof different types of cancers, such as oral cancer, pharyngeal cancer, esophagealcancer, liver cancer, colon cancer, rectal cancer and breast cancer. when ethanol isconsumed, it is mainly metabolized into carbon dioxide(CO2) through oxidativepathway and non-oxidative pathway.Ethanol metabolic process produce reactiveoxygen species (ROS),acetaldehyde adduct, consequantely induce apoptosis、necrosisand DNA damage. Chronic ethanol exposure may induce chromosomal instability.inthis assay,ethanol dosage and ethanol exposure time influence the cytotoxity andchromosomal instability (CIN) on COLO320-DM and NCM460.Then explore thealcohol toxic effect on the human genome stability further.The results showed as following:1.In COLO320-DM,the NDI under different concentrations had no significantdifference with control group;the APO of all treatment groups were significantlyhigher than the control group,and1.6%group is significantly higher than0.1%treatment group (p <0.01);the NEC of all treatment groups also significantly higherthan control, and the lowest concentration of necrosis rate was significantly lowerthan other high concentration groups (p <0.01).The CIN of all treatment groups weresignificantly higher than that of control group (p <0.01).2. In NCM460, the CIN of all treatment groups were significantly higher thanthat of control(p <0.01); the NDI of0.1—0.8%concentration groups had extremelysignificant difference with control and1.6%groups(p <0.01);the APO of alltreatment groups were higher than that of control group, and0.8、1.6%concentrationgroups had significant difference with control group (p <0.01);NEC in each treatmentgroup were higher than control group, and the other groups except0.1%treatmentgroup had significant difference with control group(p <0.01).3. Two-way ANOVA analysis the effects of ethanol dosage and ethanol exposuretime shows that the two factors had significant interactions on NDI, APO, NEC andCIN in COLO320-DM and NCM460(p <0.01);moreover, the frequency of the APO, NEC and CIN gradually increased with the increase of ethanol concentration,1.6%had the greatest effect on APO, NEC and CIN.The frequency of NDI, APO, NEC andCIN without trend as the extension of ethanol exposure time, but the contribution ofethanol exposure time on cell damage and the genetic damage is more than ethanoldosages.4. The NDI under0.1%-0.4concentration groups of COLO320-DM weresignificantly higher than that of NCM460(p <0.01); the APO under1.6%concentration of NCM460is significantly higher than COLO320-DM (p <0.01), butthere was no significant difference between the other groups.In addition, the CIN ofall groups in NCM460were significantly less than that of COLO320-DM (p <0.01).The results showed that chronic alcohol exposure induced apoptosis and necrosis,increase the frequency of MNed BNC, NBuds, NPBs, result genomic instability;.Butobvious effect on cell proliferation;chronic ethanol exposure had greater effect thanshort-term exposure to high doses of ethanol on cell damage.In addition, the genomedamage repair ability of NCM460better than COLO320-DM.