非直接基因毒性化合物对培养肝细胞中过氧化物酶体增殖和肝脏生长刺激潜能的评估。

Molecular toxicology Pub Date : 1987-09-01
F Bieri, W Stäubli, S Kelly, F Waechter, P Bentley
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引用次数: 0

摘要

在此之前,我们已经证实一些过氧化物酶体增殖物(一类非遗传毒性的肝癌物质)能够在培养的肝细胞中诱导复制性DNA合成(RDS)。短期体内治疗后观察到的肝肿大与诱导RDS的能力相关,而与体外评估的过氧化物酶体增殖剂的效力相关。为了澄清灵长类动物对过氧化物酶体增殖物的有限敏感性这一具有挑战性的问题,研究人员用纳非诺平处理狨猴肝细胞的原代培养物已有几天。正如体内观察所预期的那样,没有观察到过氧化物酶体增殖的证据。然而,nafenopin诱导RDS的量呈剂量依赖性增加,但这种诱导只有在培养基中没有血清时才能测量到。这些结果证实,过氧化物酶体增殖和有丝分裂性可能是过氧化物酶体增殖体的独立特性。由于在体内,化合物在肝细胞中诱导RDS的能力至少与致肝癌反应的一个关键参数相关,因此,在不同物种培养的肝细胞中测量RDS诱导性可能与评估非直接遗传毒性化合物在肝肿瘤效力方面的物种差异相关且有用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Assessment of peroxisome proliferation and liver growth-stimulating potential by nondirectly genotoxic compounds in cultured hepatocytes.

Previously, we have established that some peroxisome proliferators, a class of nongenotoxic hepatocarcinogens, are able to induce replicative DNA synthesis (RDS) in cultured hepatocytes. Hepatomegaly observed after short-term in vivo treatment correlated better with the ability to induce RDS than with the potency as peroxisome proliferator assessed in vitro. To clarify the challenging question of the limited sensitivity of primates to peroxisome proliferators, primary cultures of marmoset hepatocytes have been treated with nafenopin for some days. As expected from in vivo observations, no evidence for peroxisome proliferation could be observed. However, nafenopin induced a dose-dependent increase in the amount of RDS, but this induction was measurable only when the serum was absent from the culture medium. These results confirm that peroxisome proliferation and mitogenicity might be independent properties of peroxisome proliferators. Since in vivo the ability of compounds to induce RDS in liver cells is relevant to at least one key parameter of the hepatocarcinogenic response, it is suggested that measurement of RDS inducibility in cultured hepatocytes from different species might be relevant and useful to assess species differences in the liver tumor potency of nondirectly genotoxic compounds.

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