Graem N
Cancer Res. 1986 Jan;46(1):278-84.
Effects of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) and of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on epidermis of human fetal and adult skin were studied in the nude mouse/human skin model. Human skin grafts on NC nude mice were exposed to two topical applications of 1 mg of DMBA in 50 microliter of acetone with an interval of 3 days and/or to applications of 10 micrograms of TPA in 50 microliter of acetone twice weekly. In some animals, it was attempted to augment the susceptibility of the grafts to the tumor-initiating effect of DMBA by pretreatment with TPA or ultraviolet light. The mice were sacrificed 8-32 wk after the initial treatment. Tumors did not appear in the central portions of any of the grafts, but epidermal tumors were seen at the graft border in 34.9% of the DMBA-treated animals. To identify human epidermis on the grafts and to determine the species origin of the induced tumors, two independently working histological marker methods were applied. (a) The first is detection of a human Blood Group B-like antigen present in mouse epidermis and in chemically induced murine epidermal tumors. This antigen cannot be demonstrated in human epidermis and in epidermal tumors of human patients. (b) The second is histological staining with the DNA-specific fluorochrome, bisbenzimide, displaying a characteristic pattern of 5-10 intranuclear fluorescent bodies in murine nonneoplastic epidermal cells and in murine epidermal tumor cells. Such a pattern is not seen in human epidermis and in epidermal tumors of human patients. The studies showed that TPA treatment resulted in epidermal hyperplasia in both the human epidermis and the adjacent mouse epidermis and that the induced tumors were derived from murine tissue. The mechanisms behind the DMBA action in the nude mouse/human skin model are discussed, and suggestions for future carcinogenesis studies on the model are given.
在裸鼠/人皮肤模型中，研究了肿瘤引发剂7,12-二甲基苯并(a)蒽（DMBA）和肿瘤促进剂12-O-十四酰佛波醇-13-乙酸酯（TPA）对人胎儿和成人皮肤表皮的影响。将NC裸鼠身上的人皮肤移植物暴露于两次局部涂抹含1 mg DMBA的50微升丙酮中，间隔3天，和/或每周两次涂抹含10微克TPA的50微升丙酮。在一些动物中，尝试通过用TPA或紫外线预处理来增强移植物对DMBA肿瘤引发作用的敏感性。在初次治疗后8 - 32周处死小鼠。在任何移植物的中央部分均未出现肿瘤，但在34.9%接受DMBA治疗的动物的移植物边缘可见表皮肿瘤。为了识别移植物上的人表皮并确定诱导肿瘤的物种来源，应用了两种独立的组织学标记方法。（a）第一种是检测存在于小鼠表皮和化学诱导的小鼠表皮肿瘤中的人B血型样抗原。这种抗原在人表皮和人类患者的表皮肿瘤中无法检测到。（b）第二种是用DNA特异性荧光染料双苯甲酰亚胺进行组织学染色，在小鼠非肿瘤性表皮细胞和小鼠表皮肿瘤细胞中显示出5 - 10个核内荧光体的特征模式。在人表皮和人类患者的表皮肿瘤中未见这种模式。研究表明，TPA处理导致人表皮和相邻小鼠表皮出现表皮增生，且诱导的肿瘤源自鼠组织。讨论了裸鼠/人皮肤模型中DMBA作用背后的机制，并给出了关于该模型未来致癌研究的建议。
