杂色曲霉素和脱氧雪腐镰刀菌烯醇对小鼠致癌作用的研究

Carcinogenic effects of Sterigmatocystin and Deoxynivalenol in NIH mice

目的探讨杂色曲霉素(ST)对NIH小鼠的致癌作用,同时研究脱氧雪腐镰刀菌烯醇(DON)对ST致癌作用的影响。方法将180只NIH小鼠随机分为ST3μg/kg组、ST30μg/kg组、ST3μg/kg+DON1.5μg/kg组、ST30μg/kg+DON1.5μg/kg组、DON1.5μg/kg组和对照组等6组,每组30只。各实验组按要求分别灌喂不同剂量的真菌毒素,对照组灌喂同等容量的生理盐水,3次/周,共24周。实验第58周和第74周处死小鼠,观察各器官组织病变。结果对照组小鼠各器官组织均未见明显病理改变。ST和DON处理组均有部分小鼠发生肺腺癌和腺胃黏膜上皮异型增生。ST3μg/kg组、ST30μg/kg组、ST3μg/kg+DON1.5μg/kg组、ST30μg/kg+DON1.5μg/kg组和DON1.5μg/kg组肺癌的发生率分别为25.0%、41.7%、62.5%、69.2%和37.5%,腺胃黏膜上皮异型增生发生率分别为50.0%、58.3%、37.5%、53.8%和25.0%。结论经口灌喂ST和DON可诱发NIH小鼠肺癌和腺胃黏膜异型增生。ST加DON可明显提高肺癌的发生率。

Objective To further explore the carcinogenic activity of Sterigmatocystin (ST) and the possible synergistic carcinogenic effect of deoxynivalenol (DON) in NIH mice. Methods NIH mice were randomly divided into 6 groups, 30 in each. Five groups of mice were given by gastric intubation ST 3 μg/kg, ST 30 μg/kg, ST 3 μg/kg+DON 1.5 μg/kg, ST 30 μg/kg+DON 1.5 μg/kg and DON 1.5 μg/kg respectively, ~3 times a week for 24 weeks. The remaining group of mice was given normal saline accordingly, serving as control. All mice were fed with HPLC-confirmed mycotoxin-free food, analysis. The mice were killed and pathologically examined at 58~th and 74~th weeks. Results No pathological changes were found in the control group of mice. Adenocarcinoma of lung was observed in 25.0%, 41.7%, 62.5%, 69.2% and 37.5% of mice given ST 3 μg/kg, ST 30 μg/kg, ST 3 μg/kg+DON 1.5 μg/kg, ST 30 μg/kg+DON 1.5 μg/kg and DON 1.5 μg/kg, respectively. In addition, dysplasia of glandular stomach was detected in 50.0%, 58.3%, 37.5%, 53.8% and 25.0% of mice similarly treated. Conclusion Oral adminstration of ST or DON can induce adenocarcinoma in lung and dysplasia of glandular stomach in NIH mice. There is synergistic carcinogenic effect when both ST and DON are given.