Title
7,12-Dimethylbenz[a]anthracene exposure induces the DNA repair response in neonatal rat ovaries
Campus Units
Animal Science
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
11-1-2013
Journal or Book Title
Toxicology and Applied Pharmacology
Volume
272
Issue
3
First Page
690
Last Page
696
DOI
10.1016/j.taap.2013.08.013
Abstract
7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all stages of development. This study investigated DMBA-induced DNA double strand break (DSB) formation with subsequent activation of the ovarian DNA repair response in models of pre-antral or pre-ovulatory follicle loss. Postnatal day (PND) 4 Fisher 344 (F344) rat ovaries were cultured for 4 days followed by single exposures of vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and maintained in culture for 4 or 8 days. Alternately, PND4 F344 rat ovaries were exposed to 1 μM DMBA at the start of culture for 2 days. Total RNA or protein was isolated, followed by qPCR or Western blotting to quantify mRNA or protein level, respectively. γH2AX and phosphorylated ATM were localized and quantified using immunofluorescence staining. DMBA exposure increased caspase 3 and γH2AX protein. Additionally, DMBA (12.5 nM and 1 μM) increased levels of mRNA encoding Atm, Xrcc6, Brca1 and Rad51. In contrast, Parp1 mRNA was decreased on d4 and increased on d8 of DMBA exposure, while PARP1 protein increased after 8 days of DMBA exposure. Total ATM increased in a concentration-dependent temporal pattern (75 nMd4; 12.5 nMd8), while pATM was localized in large primary and secondary follicles and increased after 8 days of 75 nM DMBA exposure compared to both control and 12.5 nM DMBA. These findings support that, despite some concentration effects, DMBA induces ovarian DNA damage and that DNA repair mechanisms are induced as a potential mechanism to prevent follicle loss.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Copyright Owner
Elsevier Inc.
Copyright Date
2013
Language
en
File Format
application/pdf
Recommended Citation
Ganesan, Shanthi; Bhattacharya, Poulomi; and Keating, Aileen F., "7,12-Dimethylbenz[a]anthracene exposure induces the DNA repair response in neonatal rat ovaries" (2013). Animal Science Publications. 484.
https://lib.dr.iastate.edu/ans_pubs/484
Comments
This is a manuscript of an article published as Ganesan, Shanthi, Poulomi Bhattacharya, and Aileen F. Keating. "7, 12-Dimethylbenz [a] anthracene exposure induces the DNA repair response in neonatal rat ovaries." Toxicology and applied pharmacology 272, no. 3 (2013): 690-696. doi: 10.1016/j.taap.2013.08.013. Posted with permission.