Newcomb E W, Corominas M, Bayona W, Pellicer A
Department of Pathology, New York University Medical Center, NY 10016.
Anticancer Res. 1989 Sep-Oct;9(5):1407-15.
An animal model of carcinogenesis has been exploited to analyze the various events involved in carcinogen-induced T cell lymphomagenesis. Two carcinogenic agents, the alkylating agent N-methylnitrosourea (NMU) and ionizing gamma-radiation, induce tumors in C57BL/6J mice that are phenotypically and histologically identical. Are the genetic events similar or different in the T cell tumors produced by these two carcinogenic agents? NMU treatment produced a different spectrum of activated oncogenes from gamma-irradiation. The K-ras oncogene was preferentially activated in all of the NMU-induced tumors, most frequently by a GGT to GAT transition in codon 12. Ionizing gamma-radiation produced two different transforming activities. Approximately half of the radiation-induced tumors contained activated N-ras genes and half contained a novel non-ras transforming activity. Analysis of NMU- and gamma-irradiated treated animals for chromosomal abnormalities showed anomalies early in the disease. Although both agents produce tumors containing trisomy of chromosome 15, the timing of this event appears to be different occurring early in NMU-induced tumors and later in gamma-radiation induced tumors. In addition, a unique marker chromosome consisting of a translocation between chromosomes one and five appears to be involved in the early stages of radiation-induced disease and may be associated with the novel transforming activity detected in these same tumors. Expression of receptors for the T cell growth factor (IL-2R) is similar in both NMU- and gamma-irradiation induced tumors. Changes in the expression of IL-2R on different T cell populations with disease progression may account for thymus dependent and thymus independent phases of malignant T cell growth.
一种致癌作用的动物模型已被用于分析致癌物诱导的T细胞淋巴瘤发生过程中涉及的各种事件。两种致癌剂，烷基化剂N-甲基亚硝基脲（NMU）和电离γ辐射，可在C57BL/6J小鼠中诱导出表型和组织学上相同的肿瘤。这两种致癌剂产生的T细胞肿瘤中的遗传事件是相似还是不同呢？NMU处理产生的活化癌基因谱与γ辐射不同。K-ras癌基因在所有NMU诱导的肿瘤中优先被激活，最常见的是密码子12处的GGT到GAT转换。电离γ辐射产生两种不同的转化活性。大约一半的辐射诱导肿瘤含有活化的N-ras基因，另一半含有一种新的非ras转化活性。对接受NMU和γ辐射处理的动物进行染色体异常分析显示，在疾病早期就出现了异常。虽然两种试剂都产生含有15号染色体三体的肿瘤，但这一事件发生的时间似乎不同，在NMU诱导的肿瘤中发生得早，在γ辐射诱导的肿瘤中发生得晚。此外，一种由1号和5号染色体之间的易位组成的独特标记染色体似乎参与了辐射诱导疾病的早期阶段，并且可能与在这些相同肿瘤中检测到的新转化活性有关。T细胞生长因子（IL-2R）受体在NMU和γ辐射诱导的肿瘤中的表达相似。随着疾病进展，不同T细胞群体上IL-2R表达的变化可能解释了恶性T细胞生长的胸腺依赖性和胸腺非依赖性阶段。
