Hulla J E, French J E, Dunnick J K
University of North Dakota School of Medicine, Grand Forks, ND, USA.
Toxicol Sci. 2001 Apr;60(2):264-70. doi: 10.1093/toxsci/60.2.264.
C57BL/6 p53 (+/-) N5 mice heterozygous for a null p53 allele were given phenolphthalein to learn more about mechanisms of carcinogenesis and to evaluate the p53-deficient mouse as a tool for identifying potential human carcinogens. DNA samples isolated from 10 phenolphthalein-induced thymic lymphomas were analyzed for loss of heterozygosity (LOH) at the Trp53 locus and simple sequence length polymorphic (SSLP) loci. The initial screening revealed remarkable results from only chromosome 11. Allelotyping at approximately five centiMorgan intervals, we found SSLP heterozygosity for C57BL/6 and 129Sv over much of chromosome 11. In the tumors, treatment-related LOH was apparent on chromosome 11 at each of the 28 informative loci examined. The strain-specific polymorphism lost from individual tumors allowed us to deduce the distribution of alleles along the length of the maternal and paternal chromosomes 11. The allelic patterns indicate that mitotic homologous recombination occurred during embryogenesis if breeding protocols were carried out as described. The mitotic recombination observed may be attributable to p53 haploinsufficiency for normal suppression of mitotic recombination.
将携带无效p53等位基因杂合子的C57BL/6 p53(+/-) N5小鼠给予酚酞，以更多地了解致癌机制，并评估p53缺陷小鼠作为鉴定潜在人类致癌物工具的作用。对从10个酚酞诱导的胸腺淋巴瘤中分离的DNA样本进行分析，以检测Trp53基因座和简单序列长度多态性(SSLP)基因座的杂合性缺失(LOH)。初步筛选仅在11号染色体上发现了显著结果。以大约5厘摩的间隔进行等位基因分型，我们发现在11号染色体的大部分区域，C57BL/6和129Sv存在SSLP杂合性。在肿瘤中，在所检测的28个信息位点中的每一个位点，11号染色体上都明显存在与治疗相关的LOH。从单个肿瘤中丢失的品系特异性多态性使我们能够推断出母本和父本11号染色体上沿长度方向的等位基因分布。等位基因模式表明，如果按照所述的育种方案进行操作，有丝分裂同源重组在胚胎发育过程中发生。观察到的有丝分裂重组可能归因于p53单倍剂量不足对有丝分裂重组的正常抑制作用。
