Abstract
Complex DNA damage may manifest in double-strand breaks (DSBs) and non-DSB, bistranded, oxidatively induced clustered DNA lesions (OCDLs). Although the carcinogen benzo[α]pyrene (B[α]P) has been shown to induce chromosomal aberrations and transformation of mammary cells, it is not known whether this compound engenders clustered DNA damage. Normal primary breast tissue-derived cells were treated with B[α]P, and the levels of DNA lesions, chromosomal aberrations, total antioxidant capacity (TAC), and reactive oxygen species (ROS) were determined. DNA from cells treated with 2 and 8 µM B[α]P exhibited increases of 3- and 4-fold in APE1 ( p < 0.001), 11- and 19-fold in Endo III ( p < 0.001), and 8- and 15-fold in hOGG1 ( p < 0.001) OCDLs, respectively, compared to the 0 µM B[α]P-treated (control) group. Mammary cells treated with 8 µM B[α]P produced 0.12 aberrations per cell ( p < 0.05) and there was a strong positive correlation ( r = 0.91) between the levels of OCDLs and those of chromosomal aberrations. Finally, TAC was decreased by 25% ( p < 0.02), whereas ROS production increased by 2-fold ( p < 0.02) in cells treated with 8 μM B[α]P compared to the control group. In conclusion, oxidatively induced clustered DNA damage mediated through differential expression of APE1, reduced TAC, and increased ROS may play a significant role in the chemically induced transformation of normal primary mammary cells.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
