目的　在人乳头状瘤病毒 (HPV) 18E6E7基因诱导人胚食管上皮细胞永生化的基础上 ,观察高、低剂量丁酸钠在细胞恶性转化过程中的促癌作用。方法　永生化食管上皮细胞SHEE先用高剂量丁酸钠 (80mmol/L) ,后用低剂量丁酸钠 (5mmol/L)各处理 8周 ,再经无丁酸钠条件继续培养 14周。用相差显微镜、免疫组织化学SABC法和流式细胞仪检查细胞形态、增殖和凋亡状况 ;用Hoechst33342和碘化丙啶检查活细胞和死细胞 ;细胞软琼脂集落形成及移植裸小鼠和严重联合免疫缺陷小鼠检查成瘤性。结果　当细胞暴露在 80mmol/L丁酸钠 ,细胞死亡 ,只剩少量活细胞。在含 5mmol/L丁酸钠培养基中细胞出现第一增殖期 ;撤去丁酸钠 ,细胞进入危象期 ,细胞倍增时间延长 ,如老化细胞。度过危象期 ,细胞进入第二增殖期 ,细胞继续增生和异型增生。在第二增殖期末细胞出现恶变 ,软琼脂培养有大集落形成 ,移植裸小鼠和SCID小鼠成瘤。结论　SHEE永生化上皮由丁酸钠诱导的恶性变通过了两个阶段的死亡威胁 :高浓度丁酸钠引起细胞死亡 ,缺乏丁酸钠引起细胞危象。高剂量丁酸钠引起永生化细胞死亡 ,低剂量引起细胞增殖 ,说明丁酸钠对体外培养细胞有促恶变作用 Objective To observe the carcinogenesis of high and low doses of sodium butyrate in the process of cell malignant transformation based on the human papillomavirus (HPV) 18E6E7 gene induced immortalization of human embryo esophageal epithelial cells. Methods SHEE of immortalized esophageal epithelial cells was treated with high dose of sodium butyrate (80mmol / L) and then with low dose of sodium butyrate (5mmol / L) for 8 weeks, then cultured for 14 weeks without sodium butyrate. Cell morphology, proliferation and apoptosis were examined by phase-contrast microscopy, immunohistochemical SABC and flow cytometry; viable cells and dead cells were examined by Hoechst 33342 and propidium iodide; soft agar colony formation and transplantation of nude mice and severe Combined immunodeficiency mice were examined for tumorigenicity. Results When cells were exposed to 80 mmol / L sodium butyrate, the cells died, leaving only a small amount of viable cells. In 5mmol / L sodium butyrate medium cells appear the first proliferation period; withdrawal of sodium butyrate, the cells into the crisis period, the cell doubling time, such as aging cells. Through the crisis period, the cells into the second proliferative phase, the cells continue to proliferate and dysplasia. In the second proliferative phase cells appear malignant transformation, soft agar culture colony formation, transplantation of nude mice and SCID mice tumor. Conclusions Sodium butyrate-induced malignancy of the SHEE immortalized epithelium passes the two-stage death threat: high concentrations of sodium butyrate cause cell death and lack of sodium butyrate causes cell crisis. High-dose sodium butyrate caused immortalized cell death and low-dose induced cell proliferation, indicating that sodium butyrate has a pro-malignant effect on cultured cells in vitro