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Cited by 284

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DNA base modifications in chromatin of human cancerous tissues

Olinski, Ryszard, Zastawny, Tomasz, Budzbon, Jaroslaw, Skokowski, Jan, Zegarski, Wojtek, Dizdaroglu, Miral·1992·FEBS Letters

Abstract

Free radical‐induced damage to DNA in vivo is implicated to play a role in carcinogenesis. Evidence exists that DNA damage by endogenous free radicals occurs in vivo, and there is a steady‐state level of free radical‐modified bases in cellular DNA. We have investigated endogenous levels of typical free radical‐induced DNA base modifications in chromatin of various human cancerous tissues and their cancer‐free surrounding tissues. Five different types of surgically removed tissues were used, namely colon, stomach, ovary, brain and lung tissues. In chromatin samples isolated from these tissues, five pyrimidine‐derived and six purine‐derived modified DNA bases were identified and quantitated by gas chromatography/mass spectrometry with selected‐ion monitoring. These were 5‐hydroxy‐5‐methylhydantoin, 5‐hydroxyhydantoin, 5‐(hydroxymethyl)uracil, 5‐hydroxycytosine, 5,6‐dihydroxycytosine, 4,6‐diamino‐5‐formamidopyrimidine, 8‐hydroxyadenine, xanthine, 2‐hydroxyadenine, 2,6‐diamino‐4‐hydroxy‐5‐formamidopyrimidine, and 8‐hydroxyguanine. These compounds are known to be formed typically by hydroxyl radical attack an DNA bases. In all cases, elevated amounts over control levels of modified DNA bases were found in cancerous tissues. The amounts modified bases depended on the tissue type. Lung tissues removed from smokers had the highest increases of modified bases above the control levels, and the highest overall amounts. Colon cancer tissue samples had the lowest increases of modified buses over the control levels. The results clearly indicate higher steady‐state levels of modified DNA bases in cancerous tissues than in their cancer‐free surrounding tissues. Some of these lesions are known to be promutagenic, although others have not been investigated for their mutagenicity. Identified DNA lesions may play a causative role in carcinogenesis.

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Metadata

Authors
Olinski, R., Zastawny, T., Budzbon, J., Skokowski, J., Zegarski, W., & Dizdaroglu, M.
Venue
FEBS Letters
Publisher
Wiley
Published
1992-09-07
Volume
309
Issue
2
Pages
193-198
ISSN
  • 0014-5793 (ISSN-L)
  • 1873-3468
OpenAlex
W2089510123
Cited by
284
References
1
FWCI
6.32
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: DNA base modifications in chromatin of human cancerous tissues. https://app.cochat.ai/papers/10.1016/0014-5793(92)81093-2
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Olinski, R., Zastawny, T., Budzbon, J., Skokowski, J., Zegarski, W., & Dizdaroglu, M. (1992). DNA base modifications in chromatin of human cancerous tissues. FEBS Letters. https://doi.org/10.1016/0014-5793(92)81093-2

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