Major effect on susceptibility to urethan-induced pulmonary adenoma by a single gene in BALB/cBy mice.
Major effect on susceptibility to urethan-induced pulmonary adenoma by a single gene in BALB/cBy mice.
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DOI：
10.1093/jnci/70.5.931
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发表时间：
1983-05
期刊：
影响因子：
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通讯作者：
A. Malkinson;D. S. Beer
中科院分区：
文献类型：
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作者：
A. Malkinson;D. S. Beer
与A/J或SWR/J小鼠相比，尿素诱发的BALB/CBY小鼠肺腺瘤较少。当BALB小鼠与这些更敏感的菌株中的任何一种杂交时，后代对尿素的反应最容易用调节敏感性的单个基因来解释，更具抗性的表型表现为显性特征。C56BL/6J小鼠对腺瘤诱导的抵抗力强于BALB小鼠；这两个品系杂交得到的后代与BALB小鼠的易感表型相似。为了了解该基因的作用机制，在BALB小鼠和其他菌株中测试了调节腺瘤启动和肿瘤促进的药物。BALB小鼠体内腺瘤的数量通过多次注射乌拉坦(可能影响启动)和使用丁基化邻羟基甲苯作为促进剂而增加几倍。每种治疗方法均可使A系小鼠的肿瘤发病率增加50%；两种方法均未导致耐药株DBA/2J、C3H/-21BG或C57BL/6J出现肿瘤。没有观察到这些药物多次注射致死效应的菌株依赖性与这些菌株对腺瘤诱导的相对易感性之间的关系。还检测了某些宿主因素在肿瘤易感性调节中的作用。米色(BG)突变的纯合性对C57小鼠的肿瘤数量没有影响，这表明BG/BG小鼠缺乏的自然杀伤细胞在决定该品系的腺瘤易感性方面没有主要作用。未发现不同亚系对乌拉坦诱导的肺腺瘤的敏感性与这些亚系的腹膜巨噬细胞的相对杀瘤能力之间的相关性。
Fewer lung adenomas were induced by urethan in BALB/cBy mice than in the A/J or SWR/J mouse strains. When BALB mice were crossed with either of these more sensitive strains the response of the progeny to urethan was most easily explained by a single gene which regulates susceptibility, with the more resistant phenotype behaving as a dominant trait. C56BL/6J mice were more resistant to adenoma induction than were BALB mice; progeny obtained when these two strains were crossed resembled the BALB susceptibility phenotype. As an approach to understanding the mechanism of action of this gene, agents that modulate adenoma initiation and tumor promotion were tested in BALB mice and other strains. The number of adenomas in BALB mice were increased severalfold by multiple urethan injections, which presumably affect initiation, and by the use of butylated o-hydroxytoulene as a promoting agent. Tumor incidence in A-mice was increased 50% by each treatment; neither procedure caused tumors to appear in the resistant DBA/2J, C3H/-21BG, or C57BL/6J strains. No relationship was observed between the strain dependency of the lethal effects of multiple injections of these agents and the relative susceptibilities of these strains to adenoma induction. The role of certain host factors in the regulation of tumor susceptibility was also tested. Homozygosity for the beige (bg) mutation had no effect on tumor numbers in C57 mice, suggesting that natural killer cells, deficient in bg/bg mice, played no major role in determining adenoma susceptibility in this strain. No correlation was found between the susceptibility of various sublines to urethan-induced lung adenoma and the reported relative tumoricidal capacities of the peritoneal macrophages from these sublines.