Genetic predisposition to 4NQO induced tongue carcinogenesis in the rat

This study aims to elucidate the genetic basis of predisposition to 4-nitroquinoline 1-oxide [4NQO]-induced tongue cancers [TCs]. We have reported that inbred Dark-Agouti [DA] strain rats were highly susceptible to 4NQO-induced TCs, whereas Wistar/Furth [WF] rats were resistant to tongue squamous cell carcinomas induced by oral administration of 4NQO. Using size and number of the tumours as quantitative parameters, responsible host loci were analysed by an interval mapping of F2 intercross of DA and WF given carcinogenic regimen. Also, loss of heterozygosity [LOH] at these loci was analysed in tongue cancers in [DA x WF] F1. We identified and mapped 5 significant quantitative trait loci [QTL], the Tongue squamous cell carcinoma 1-5 [Tscc1-5], and several other suggestive QTL that determine susceptibility to 4NQO-induced TC. Study of TCs induced in [DA x WF]F1 rats revealed a high frequency of LOH in the chromosomal regions of Tscc2, 3, and 4 and also of suggestive QTL on chromosomes 5 and 6. The fact that LOH was found only in larger TCs indicates that LOH occurred in the process of tumour progression. In most LOH, the allele of the resistant WF strain was lost, suggesting that these loci may encode tumour suppressor genes. In larger TCs, in addition to LOH, point mutations and the methylation of possible candidate genes were accumulated. These observations indicate that the 4NQO-induced TC in the rat is a multifactorial disease of a polygenic trait. This model will be useful to understand the complicated genetic basis of predisposition to oral cancers

The effect of disuse on the human femur. A study in an aged man suffered a lower leg amputation / 体力科学

Human femora obtained from a cadaver of a 70-year-old man were examined by means of bone histometry, image-analysis on X-ray radiographs and a mechanical strength test in order to investigate the effects of disuse on the femora. The patient had been bedfast for seven months until his death because of an amputation of the left lower leg due to a diabetic intractable ulcer on the foot caused by a burn. Other detail records of the medical and the life-style history were also examined.<BR>A marked atrophy of the muscles of the hip and thigh was observed on the amputated side. The macroscopic shape and proportion of the femora were not significantly different between both sides. The results of bending strength test at the mid shaft, disclosed a marked mechanical fragility on the amputated side. The cortical bone area in the shaft showed no significant difference between both sides. However, the degree of bone loss was more pronounced at the anterior region of both shafts. The trabecular bone at the femoral head showed a marked atrophy on the amputated side, especially at the principal compressive group of the trabecular bone. This atrophy was thought to be due to the absence of the compressive stress because of the disuse caused by the amputation. A trabecular bone atrophy was also observed on the normal side and its degree of atrophy was greater than that of agematched values. The multiple systemic factors such as the diabetes and the bedfast condition might had influenced on the bone metabolism in this case, therefore the careful examination of the systemic conditions was required to disclose the effects of local mechanical conditions on the bone metabolism.