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3-甲基胆蒽与小鼠肺DNA的持续结合及其与肺肿瘤易感性的相关性。

Persistent binding of 3-methylcholanthrene to mouse lung DNA and its correlation with susceptibility to pulmonary neoplasia.

作者信息

Eastman A, Bresnick E

出版信息

Cancer Res. 1979 Jul;39(7 Pt 1):2400-5.

PMID:445439
Abstract

A/J, C3H/HeJ, DBA/2J, and C57BL/6J mice have different susceptibilities to polycyclic aromatic hydrocarbon-induced pulmonary neoplasia, whereas the livers from these animals are uniformly resistant to the carcinogenic actions of these substances. After i.v. injection of [3H]-3-methylcholanthrene, radiolabel was detected in the DNA of both lung and liver of all these strains. The DNA was digested to deoxyribonucleosides and chromatographed on Sephadex LH-20. The amounts of nucleoside-bound adducts detected varied markedly with the different tissues and strains. These adducts were undetectable in liver DNA by 28 days. Although all lung preparations showed some reduction in adducts by 28 days, the amounts in A/J lung were always highest; this correlated with its high susceptibility to neoplastic transformation. In all preparations, radioactivity eluted from Sephadex LH-20 with the column void volume or with underivatized nucleosides. Tissue, but not strain differences were observed in these chromatographic profiles. The predominance of these early-eluting peaks in liver, rather than lung, suggests that they may represent noncarcinogenic lesions. This radiolabeled material remains uncharacterized, but some possibilities are discussed.

摘要

A/J、C3H/HeJ、DBA/2J和C57BL/6J小鼠对多环芳烃诱导的肺部肿瘤形成具有不同的易感性,而这些动物的肝脏对这些物质的致癌作用均具有抗性。静脉注射[3H]-3-甲基胆蒽后,在所有这些品系的肺和肝DNA中均检测到放射性标记。将DNA消化成脱氧核糖核苷,并在Sephadex LH-20上进行色谱分析。检测到的与核苷结合的加合物数量因不同组织和品系而有显著差异。到28天时,在肝脏DNA中检测不到这些加合物。尽管所有肺组织样品在28天时加合物都有一定程度的减少,但A/J肺中的加合物数量始终最高;这与其对肿瘤转化的高易感性相关。在所有样品中,放射性物质从Sephadex LH-20上以柱空体积或未衍生化的核苷形式洗脱下来。在这些色谱图中观察到了组织差异,但没有品系差异。这些早期洗脱峰在肝脏而非肺中占优势,这表明它们可能代表非致癌性损伤。这种放射性标记物质的特性仍未明确,但讨论了一些可能性。

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