INDUCTION OF CERVICAL NEOPLASIA IN THE MOUSE BY HERPES-SIMPLEX VIRUS TYPE-2 DNA
INDUCTION OF CERVICAL NEOPLASIA IN THE MOUSE BY HERPES-SIMPLEX VIRUS TYPE-2 DNA
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DOI：
10.1073/pnas.86.12.4520
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发表时间：
1989-06-01
影响因子：
11.1
通讯作者：
HEGGIE, AD
中科院分区：
文献类型：
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作者：
ANTHONY, DD;WENTZ, WB;HEGGIE, AD
已经报道了1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（HSV-2）在小鼠宫颈中诱导宫颈瘤形成。本研究旨在观察单纯疱疹病毒2型（HSV-2）DNA转染是否能诱发肿瘤的发生。从感染的HEp-2细胞中分离基因组HSV-2 DNA，并通过氯化铯密度梯度离心从宿主细胞DNA中分离。将DNA应用于小鼠子宫颈80-100周。实验对照用未感染的基因组HEp-2细胞DNA或小牛胸腺DNA处理。每月检查所有动物的阴道细胞学标本，以检测上皮异常。当在阴道涂片上观察到指示癌前病变或恶性病变的细胞变化时，处死动物并进行组织病理学研究。对细胞学和组织学材料进行编码和评价，不知道它们是否来自病毒或对照DNA处理的动物。在暴露于HSV-2 DNA的动物中获得的组织学标本中，61%检测到类似于女性发生的癌前病变和恶性宫颈病变。在用HSV-2 DNA治疗的动物中，侵袭性癌症的发生率为21%。在用HEp-2或小牛胸腺DNA处理的小鼠中未检测到癌症。仅在这些对照动物中的一只中检测到发育不良。
induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (Hsv-1) and 2 (HSV-2) has been reported. The present study was done to detemrine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.