Effects of extracellular and intracellular pH on repair of potentially lethal damage, chromosome aberrations and DNA double-strand breaks in irradiated plateau-phase A549 cells

Journal Article · Mon Aug 01 04:00:00 EDT 1994 · Radiation Research

DOI:https://doi.org/10.2307/3578659· OSTI ID:70229

Jayanth, V R; Bayne, M T; Varnes, M E ^[1]

---

1. Case Western Reserve Univ., Cleveland, OH (United States)

Plateau-phage A549 cells exhibit a high capacity for repair of potentially lethal radiation damage (PLD). Previously it was found that PLD repair could be partially inhibited by increasing the extracellular pH (pH{sub e}) of the spent medium from its normal value of 6.7-6.8 to 7.6 during postirradiation holding. This study shows that PLD repair is also inhibited by reducing the pH{sub e} of the spent medium to 6.0. The effects of altering pH{sub e} on rejoining of DNA double-strand breaks (DSBs) as measured by neutral filter elution and on mitotic delay and chromosome aberrations seen after releasing cells from the plateau phase were investigated. Neither increasing nor decreasing the pH{sub e} of the spent medium had an effect on radiation-induced mitotic delay. Rejoining of DSBs was significantly inhibited by holding at pH{sub e} 6.0 but not affected by holding at pH{sub e} 7.6. At 2 h after irradiation about 51% of unrejoined breaks remained at pH{sub e} 6.0, compared to about 15% at pH{sub e} 6.7 or 7.6. However, holding at pH{sub e} 7.6 appeared to cause a marginal change in the kinetics of rejoining of DSBs. Repair of lesions leading to dicentric and acentric chromosome aberrations did not occur when cells were held at pH{sub e} 6.0, since less than 10% of these aberrations disappeared from cells held for 24 h before subculture. In contrast, holding plateau-phase cells at pH{sub e} 7.6 vs 6.7 caused a small but significant reduction in the disappearance of dicentrics but had no effect on the rate or extent of the disappearance of acentrics. These data have led us to hypothesize that inhibition of PLD repair by holding at pH{sub e} 6.0 is related both to inhibition of pH-dependent DNA repair enzymes and to induction of changes in DNA which lead to misrepair when the cells are released from plateau phase. Inhibition of PLD repair by holding at pH{sub e} 7.6 is related primarily to changes in DNA structure which promote misrepair. 43 refs., 5 figs., 4 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 70229
• Journal Information: Radiation Research, Journal Name: Radiation Research Journal Issue: 2 Vol. 139; ISSN RAREAE; ISSN 0033-7587
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
CHROMOSOMAL ABERRATIONS
DNA REPAIR
ENZYME ACTIVITY
LETHAL IRRADIATION
MITOTIC DELAY
PH VALUE
RESPONSE MODIFYING FACTORS
STRAND BREAKS