Robinson E S, VandeBerg J L, Hubbard G B, Dooley T P
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228.
Cancer Res. 1994 Nov 15;54(22):5986-91.
Litters of suckling young of the laboratory opossum (Monodelphis domestica) were irradiated with UV light from sunlamps with a spectral emission peak at 302 nm (UVB) to induce melanocytic nevi. Total doses of 0.87-5.0 kJ/m2 were divided equally among up to 14 exposures during the 19 days from birth. Of 358 sucklings exposed, 217 survived to weaning, and 22 (10%) possessed a nevus when shaved and examined at or after weaning. Affected animals were then exposed 3 times/week to 125 J/m2 of UVB for up to 45 weeks to promote progression to malignancy. Nevi of 8 of the 20 chronically-exposed animals progressed to malignant melanoma with metastases to lymph node(s). Cell cultures were prepared from affected nodes to confirm that pigmented nodal cells were metastatic melanomas. One established cell line (TD15L) contained highly pigmented, dendritic, malignant melanoma cells. These cells, injected s.c. as xenogeneic grafts into athymic nude mice, remained viable in the subcutis and were moderately tumorigenic in the dermis. UVR exposure of Monodelphis sucklings is a novel, effective, and proficient way of initiating melanocytic lesions for studies on susceptibility and progression to melanoma, and the cell lines derived from these melanomas will provide promising new reagents for chemotherapy and immunotherapy investigations.
用光谱发射峰值在302纳米(UVB)的太阳灯发出的紫外线照射实验室负鼠(短尾负鼠)的哺乳期幼崽,以诱导黑素细胞痣。在出生后的19天内,将0.87 - 5.0千焦/平方米的总剂量平均分配到最多14次照射中。在358只接受照射的幼崽中,217只存活到断奶,其中22只(10%)在断奶时或断奶后剃毛检查时出现了痣。然后,对受影响的动物每周3次暴露于125焦/平方米的UVB下,持续长达45周,以促进其发展为恶性肿瘤。20只长期暴露的动物中有8只的痣发展为恶性黑色素瘤,并转移至淋巴结。从受影响的淋巴结制备细胞培养物,以确认色素沉着的淋巴结细胞是转移性黑色素瘤。一个已建立的细胞系(TD15L)包含高度色素沉着、具有树突状的恶性黑色素瘤细胞。将这些细胞作为异种移植物皮下注射到无胸腺裸鼠体内,它们在皮下保持存活,并在真皮中具有中等致瘤性。对短尾负鼠幼崽进行紫外线辐射暴露是一种启动黑素细胞病变以研究黑素瘤易感性和进展的新颖、有效且熟练的方法,从这些黑色素瘤衍生的细胞系将为化疗和免疫治疗研究提供有前景的新试剂。