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How Much Should We Involve Genetic and Environmental Factors in the Risk Assessment of Mycotoxins in Humans?

机译:在人类真菌毒素的风险评估中我们应将遗传和环境因素纳入多少?

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摘要

Despite consented efforts in prevention, mycotoxins remain a problem of human health concern in several parts of the world including developed countries. Within the same range of toxins concentrations in the blood some people develop a disease while others do not. Could this inequality in front of mycotoxins effects be explained by environment factors and/or genetic predisposition? Among recent advances in environmental health research Correlation between chronic diseases and mycotoxins in humans deserves attention through several questions: Are genetic factors involved in disease causation of mycotoxins? How much are these factors currently taken into account for mycotoxins risk assessment and how much should we involve them? Answers are still to come. Genetic and environment factors deserve therefore more attention when dealing with regulatory limits, since among the general population, those who are at risk and will develop specific diseases are likely those bearing genetic predispositions. We have addressed these questions for the specific case of ochratoxin A in humans by investigating in Tunisia, county of Jelma, in four rural families forming a household of 21 persons all exposed to ochratoxin A in diet. Our results confirm that ochratoxin A induces chronic tubular nephropathy in humans and mainly point at those having the HLA haplotype A3, B27/35, DR7 to be more sensitive to the disease for quantitatively similar or lower exposure. Persons with such haplotype were found to bear chronic interstitial nephropathy with tubular karyomegalic cells while others were apparently healthy. Godin et al. (1996) in France have also found in sibling (a sister and her brother from urban area) that have similar HLA haplotype B35-patern, OTA-related renal tubulopathy with mild proteinuria including β2-microglobulinuria. Several mechanisms are discussed that could be put ahead to explain how the HLA haplotype could lead to tubular cells lyses and renal failure. In the mean time it is urgent to search for mass screening biomarkers for mycotoxins in humans and related genetic factors to set-up more appropriate regulation.
机译:尽管在预防方面已达成共识,但霉菌毒素仍是包括发达国家在内的世界上许多地区对人类健康关注的问题。在血液中毒素浓度相同的范围内,有些人会患上某种疾病,而其他人则不会。能否通过环境因素和/或遗传易感性来解释真菌毒素作用前的这种不平等?在环境卫生研究的最新进展中,人类慢性病与霉菌毒素之间的相关性应通过以下几个问题来关注:霉菌毒素的病因是否涉及遗传因素?霉菌毒素风险评估中目前考虑了这些因素有多少,我们应该涉及多少?答案仍未到。因此,在应对法规限制时,遗传和环境因素应引起更多关注,因为在一般人群中,处于危险中并会发展为特定疾病的人可能具有遗传易感性。我们已经通过在耶尔马县突尼斯的四个农村家庭中进行调查,解决了人类中och曲毒素A的特殊情况,这些家庭组成了一个由21个人组成的家庭,这些人全都暴露于饮食中的曲毒素A。我们的结果证实曲霉毒素A会诱发人类慢性肾小管肾病,并且主要针对那些具有HLA单倍型A3,B27 / 35,DR7的人,从数量上相似或更低的暴露水平来看,它对该病更为敏感。发现具有这种单倍型的人患有肾小管性巨核细胞慢性间质性肾病,而其他人显然健康。 Godin等。 (1996)在法国也发现了具有相似的HLA单倍型B35型,OTA相关的肾小管病,轻度蛋白尿症(包括β2-微球蛋白尿症)的兄弟姐妹(城市地区的一个姐妹和她的兄弟)。讨论了几种机制,可以提前解释HLA单倍型如何导致肾小管细胞溶解和肾衰竭。同时,迫切需要寻找大量筛选人类霉菌毒素的生物标志物以及相关的遗传因素,以建立更合适的调节方法。

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