Den Engelse L, Oomen L C, van der Valk M A, Hart A A, Dux A, Emmelot P
Int J Cancer. 1981 Aug 15;28(2):199-208. doi: 10.1002/ijc.2910280214.
Male mice of the strain A/Sn, of its congeneic partner strain A.SW, C57BL/10ScSnA (abbreviated: B10), and of two congeneic strains on a B10 background (B10.A and B10.AKM) were investigated for their susceptibility to lung tumour induction by dimethylnitrosamine (DMN) administered either by intraperitoneal injection or in the drinking water. Strain B10 (haplotype H-2b) proved to be very resistant, whereas strains A/Sn (H-2a) and A.SW (H-2s) were highly susceptible. The introduction of the haplotypes H-2a and H-2m in the resistant strain B10 resulted in a significant increase in sensitivity towards DMN-induced lung tumour formation. Lung tumour incidences in male (B10.A x B10)F hybrids, receiving DMN in drinking water, were found to be intermediate between, and significantly different from, the incidences of identically-treated parent strains B10.A and B10. Males of back-cross (B10.A x B10) x B10 BC proved to be of low susceptibility to lung tumour formation by DMN, tumour incidence being very low and not significantly different from that observed in identically-treated B10 males. It is concluded that, at least in the model system of B10-derived congeneic strains, H-2 haplotype is one of the factors important in determining susceptibility towards DMN-induced lung tumours. Comparison of C3Hf (H-2k), C3H/Sn (H-2k) and the latter's congeneic strains C3H.B10 (H-2b) and C3H.NB (H-2p) of male mice showed that these strains were moderately susceptible to both lung tumour and hepatoma formation by DMN. Accordingly, the presence of an H-2 haplotype from a lung-tumour-resistant strain (H-2b, B10) on the background of a strain of intermediate susceptibility (C3H) does not decrease susceptibility to lung tumour formation. The results were considered in the light of the H-2 haplotype dependence of spontaneous lung tumours, and consequently attention has been paid to the histological types of the induced and spontaneous lung tumours.
研究了A/Sn品系、其同源近交系A.SW、C57BL/10ScSnA(简称:B10)以及两个以B10为背景的同源近交系(B10.A和B10.AKM)的雄性小鼠,通过腹腔注射或饮水给予二甲基亚硝胺(DMN)诱导肺肿瘤的易感性。结果表明,B10品系(单倍型H-2b)对DMN诱导的肺肿瘤具有高度抗性,而A/Sn品系(H-2a)和A.SW品系(H-2s)则高度敏感。将单倍型H-2a和H-2m导入抗性品系B10后,对DMN诱导的肺肿瘤形成的敏感性显著增加。在饮用含DMN水的雄性(B10.A×B10)F1杂种小鼠中,肺肿瘤发生率介于相同处理的亲本品系B10.A和B10之间,且与它们有显著差异。回交(B10.A×B10)×B10 BC1雄性小鼠对DMN诱导的肺肿瘤形成敏感性较低,肿瘤发生率很低,与相同处理的B10雄性小鼠观察到的结果无显著差异。得出结论,至少在B10衍生的同源近交系模型系统中,H-2单倍型是决定对DMN诱导的肺肿瘤易感性的重要因素之一。对雄性小鼠C3Hf(H-2k)、C3H/Sn(H-2k)及其同源近交系C3H.B10(H-2b)和C3H.NB(H-2p)的比较表明,这些品系对DMN诱导的肺肿瘤和肝癌形成均具有中等易感性。因此,在中等易感性品系(C3H)背景下存在来自肺肿瘤抗性品系(H-2b,B10)的H-2单倍型,并不会降低对肺肿瘤形成的易感性。根据自发肺肿瘤对H-2单倍型的依赖性对结果进行了分析,因此关注了诱导性和自发性肺肿瘤的组织学类型。