Genomic DNA is organized three-dimensionally in the nucleus, and is thought to form compact chromatin domains. Although chromatin compaction is known to be essential for mitosis, whether it confers other advantages, particularly in interphase cells, remains unknown. Here, we report that chromatin compaction protects genomic DNA from radiation damage. Using a newly developed solid-phase system, we found that the frequency of double-strand breaks (DSBs) in compact chromatin after ionizing irradiation was 5–50-fold lower than in decondensed chromatin. Since radical scavengers inhibited DSB induction in decondensed chromatin, condensed chromatin had a lower level of reactive radical generation after ionizing irradiation. We also found that chromatin compaction protects DNA from attack by chemical agents. Our findings suggest that genomic DNA compaction plays an important role in maintaining genomic integrity.

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A high-quality Si−MCM-41 was prepared with the composition of SiO2, 0.2; TEAOH, 0.25; CTMABr, 35 in H2O using fumed silica as the silica source. The quality of the compounds was assessed using different analytical techniques such as XRD, N2 adsorption−desorption measurement, UV−vis absorption, FTIR, and 29Si MAS NMR. The quality of M41S mesoporous materials, synthesized using a single C16TMA+ surfactant, could be further improved by a postsynthesis hydrothermal treatment of the as-synthesized materials in water. In comparison with the ordinary preparation, the water-treated materials exhibited a higher long-distance order, a higher BET surface area, and a larger pore size. The postsynthesis water treatment method provided an easy and mild way to prepare high-quality M41S molecular sieves with the pore size controllable by altering either the treatment time or the temperature. The postsynthesis treatment also enhanced the stability, especially the hydrothermal stability, of Si−MCM-41. The 29Si MAS NMR results demonstrated that the water treatment promoted the wall polymerization or local atomic arrangement. It was suggested that the pH lowering of synthesis mixture by replacing the mother liquor with water played a crucial role in the restructuring toward a high-quality Si−MCM-41. The quality of Ti−MCM-41, Al−MCM-41, and Si−MCM-48 was also improved by a similar postsynthesis hydrothermal treatment.

Ferric nitrilotriacetate (Fe-NTA) causes renal proximal tubular necrosis, a consequence of iron ion-mediated free-radical-associated damage, that finally leads to a high incidence of renal adenocarcinoma in male rats and mice. We have investigated the levels of typical hydroxyl radical-induced DNA base modifications in renal chromatin of male Wistar rats treated with a single or repeated administrations of Fe-NTA. Five pyrimidine-derived and 5 purine-derived modified DNA bases were identified and quantified by gas chromatography/mass spectrometry with selected-ion monitoring. The modified bases were 5-hydroxy-5-methylhydantoin, 5-(hydroxymethyl)uracil, 5-hydroxycytosine, thymine glycol, 5,6-dihydroxyuracil, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, xanthine, 2-hydroxyadenine and 8-hydroxyguanine. The amounts of most of these compounds were significantly increased over control levels in renal chromatin of Fe-NTA-treated rats as measured 3 and 24 hr after treatment. Elevated levels of modified bases were accompanied by proximal tubular necrosis. On the 19th day, however, accumulation of modified DNA bases was not observed. Morphologically, scattered karyomegalic cells were seen in the proximal tubules, but necrosis was rarely found. Some of the identified DNA base lesions are known to be promutagenic, although others have not been investigated. Presence of modified DNA bases concomitant with necrosis and regeneration of the renal proximal tubules may be a critical step in Fe-NTA-induced carcinogenesis.