Acidic cellular microenvironment modifies carcinogen-induced DNA damage and repair

Area of Science:

• Environmental Science
• Biochemistry
• Molecular Biology

Background:

• Chronic inflammation is linked to cancer development.
• Acidic microenvironments are a hallmark of inflammation.
• The impact of low pH on carcinogen response is not fully understood.

Purpose of the Study:

• To investigate how acidic conditions affect cellular responses to benzo[a]pyrene (B[a]P).
• To examine the influence of extracellular pH (pH_e) on B[a]P metabolism, DNA repair, and adduct formation.

Main Methods:

• Human pulmonary epithelial cells (A549, BEAS-2B) were exposed to B[a]P in media with varying pH (7.8 to 5.5).
• B[a]P metabolism, cytochrome P450 activity, DNA repair, and B[a]P-DNA adducts were measured at 6, 24, and 48 hours.
• Intracellular and extracellular pH were monitored throughout the incubations.

Main Results:

• Acidic pH (below 6.0) delayed B[a]P metabolism and reduced cytochrome P450 activity initially.
• DNA repair incision activity was significantly inhibited at low pH.
• After 48 hours, acidic conditions led to higher B[a]P-DNA adduct levels and γ-H2AX foci.

Conclusions:

• Acidic microenvironments delay carcinogen metabolism and impair DNA repair mechanisms.
• This delay and impairment result in increased B[a]P-induced DNA damage.
• The findings highlight the role of pH in modulating cellular responses to environmental carcinogens.