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吸入氡对Wistar大鼠、叙利亚仓鼠和中国仓鼠体内肺成纤维细胞的遗传毒性。

Inhaled radon-induced genotoxicity in Wistar rat, Syrian hamster, and Chinese hamster deep-lung fibroblasts in vivo.

作者信息

Khan M A, Cross F T, Buschbom R L, Brooks A L

机构信息

Pacific Northwest Laboratory, Richland, WA 99352, USA.

出版信息

Mutat Res. 1995 Apr;334(2):131-7. doi: 10.1016/0165-1161(95)90003-9.

Abstract

This study was performed (1) to provide a comparison of the genotoxic effects of inhaled radon and radon progeny, referred to as radon in this paper, among three species of rodents: Wistar rats, Syrian hamsters, and Chinese hamsters; (2) to determine if initial chromosome damage was related to the risk of induction of lung cancer; and (3) to evaluate the tissue repair and long-term presence of cytogenetic damage in respiratory tract cells. These species were selected because Syrian hamsters are very resistant to radon induction of lung cancer and Wistar rats are sensitive; no literature is available on the in vivo effects of radon in the Chinese hamster. Exposure-response relationships were established for the rats and Syrian hamsters while the Chinese hamsters received a single exposure of radon. At 4 h (0.2 days), 15 days, and 30 days after the highest WLM exposure to radon, Wistar rats, Chinese hamsters, and Syrian hamsters were killed, and lung fibroblasts were isolated and grown in culture to determine the frequency of induced micronuclei. Animals at each level of exposure showed an increase in the frequency of micronuclei relative to that in controls (P < 0.05). The exposure-response relationship data for rats and Syrian hamsters killed 0.2 days after the end of exposure were fit to linear equations (micronuclei/1000 binucleated cells = 15.5 +/- 14.4 + 0.53 +/- 0.06 WLM and 38.3 +/- 15.1 + 0.80 +/- 0.08 WLM, respectively). For the single exposure level used (496 WLM) in Chinese hamsters killed at 0.2 days after exposure, the frequency of micronuclei/1000 binucleated cells/WLM was 1.83 +/- 0.02. A comparison of the sensitivity for induction of micronuclei/WLM illustrated that Chinese hamsters were three times more sensitive than rats. The Syrian hamsters also showed a significantly elevated response (P < 0.05) relative to rats. These data suggest that initial chromosome damage is not the major factor responsible for the high rate of radon-induced cancer in rats relative to Syrian hamsters. The frequency of micronuclei in radon-exposed rats, Syrian hamsters, and Chinese hamsters significantly decreased (P < 0.05) as a function of time after the exposure. The rate of loss of damaged cells from the lung was greatest in the Chinese hamsters, followed by Wistar rats and Syrian hamsters, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

本研究旨在

(1)比较吸入氡及其子体(本文中统称为氡)对三种啮齿动物(Wistar大鼠、叙利亚仓鼠和中国仓鼠)的遗传毒性作用;(2)确定初始染色体损伤是否与肺癌诱发风险相关;(3)评估呼吸道细胞的组织修复及细胞遗传损伤的长期存在情况。选择这些物种是因为叙利亚仓鼠对氡诱发肺癌具有很强的抗性,而Wistar大鼠则较为敏感;关于氡对中国仓鼠体内作用的文献尚无报道。为大鼠和叙利亚仓鼠建立了暴露-反应关系,而中国仓鼠接受单次氡暴露。在最高氡暴露工作水平月(WLM)后的4小时(0.2天)、15天和30天,处死Wistar大鼠、中国仓鼠和叙利亚仓鼠,分离肺成纤维细胞并进行培养,以确定诱导微核的频率。各暴露水平的动物相对于对照组,微核频率均有所增加(P<0.05)。暴露结束后0.2天处死的大鼠和叙利亚仓鼠的暴露-反应关系数据符合线性方程(微核/1000双核细胞=15.5±14.4+0.53±0.06 WLM和38.3±15.1+0.80±0.08 WLM)。对于暴露后0.2天处死的中国仓鼠所采用(496 WLM)的单次暴露水平,微核/1000双核细胞/WLM频率为1.83±0.02。微核诱导/WLM敏感性的比较表明,中国仓鼠比大鼠敏感三倍。叙利亚仓鼠相对于大鼠也表现出显著升高的反应(P<0.05)。这些数据表明,相对于叙利亚仓鼠,初始染色体损伤并非大鼠中氡诱发癌症高发生率的主要因素。氡暴露的大鼠、叙利亚仓鼠和中国仓鼠中的微核频率在暴露后的一段时间内显著降低(P<0.05)。受损细胞从肺中丢失的速率在中国仓鼠中最大,其次分别是Wistar大鼠和叙利亚仓鼠。(摘要截断于400字)

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