Induction by 7,12-dimethylbenz(a)anthracene of molecular and biochemical alterations in transformed human mammary epithelial stem cells, and protection by N-acetylcysteine

  • Authors:
    • Silvio De Flora
    • Sonia Scarfì
    • Alberto Izzotti
    • Francesco D'Agostini
    • Chia-Cheng Chang
    • Maria Bagnasco
    • Antonio De Flora
    • James E. Trosko
  • View Affiliations

  • Published online on: September 1, 2006     https://doi.org/10.3892/ijo.29.3.521
  • Pages: 521-529
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Several lines of evidence suggest that stem cells are major targets for carcinogens. A normal human breast epithelial cell type was previously shown to possess stem cell characteristics. Further cell lines were derived following sequential transfection with SV40 large T-antigen (immortal, non-tumorigenic M13SV1 cells), exposure to X-rays (weakly tumorigenic M13SV1R2 cells), and ectopic expression of c-erbB2/neu (highly tumorigenic M13SV1R2N1 cells). We evaluated some characteristics of these cells and their susceptibility to the breast carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Compared to M13SV1 cells, the two untreated tumorigenic cell lines displayed higher levels of connexin 43 expression and NF-κB nuclear translocation, and a higher frequency of fhit loss. The baseline nuclear translocation of AP-1 and pCREB was particularly evident in M13SV1R2N1 cells and was further enhanced by DMBA treatment, indicating an interaction between c-erbB2/neu and DMBA-induced signalling. Treatment with DMBA did neither affect the baseline fhit loss nor p53 mutation, whereas it increased NF-κB nuclear translocation, the proportion of apoptotic cells, and the levels of connexin 43, common 4977-bp mitochondrial DNA deletion, and bulky adducts to nuclear DNA. DMBA-treated M13SV1 cells underwent significant oxidative DNA damage and exhibited the highest DNA adduct levels, while they had the lowest apoptotic rate. Co-treatment of cells with N-acetylcysteine (NAC) attenuated DMBA-induced toxicity and DNA alterations, particularly in M13SV1 cells. Thus, the immortal cell line derived from the normal human adult breast stem cell without further tumorigenic progression is the most susceptible both to DMBA-related alterations and to the protective effects of NAC.

Related Articles

Journal Cover

September 2006
Volume 29 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
De Flora, S., Scarfì, S., Izzotti, A., D'Agostini, F., Chang, C., Bagnasco, M. ... Trosko, J.E. (2006). Induction by 7,12-dimethylbenz(a)anthracene of molecular and biochemical alterations in transformed human mammary epithelial stem cells, and protection by N-acetylcysteine. International Journal of Oncology, 29, 521-529. https://doi.org/10.3892/ijo.29.3.521
MLA
De Flora, S., Scarfì, S., Izzotti, A., D'Agostini, F., Chang, C., Bagnasco, M., De Flora, A., Trosko, J. E."Induction by 7,12-dimethylbenz(a)anthracene of molecular and biochemical alterations in transformed human mammary epithelial stem cells, and protection by N-acetylcysteine". International Journal of Oncology 29.3 (2006): 521-529.
Chicago
De Flora, S., Scarfì, S., Izzotti, A., D'Agostini, F., Chang, C., Bagnasco, M., De Flora, A., Trosko, J. E."Induction by 7,12-dimethylbenz(a)anthracene of molecular and biochemical alterations in transformed human mammary epithelial stem cells, and protection by N-acetylcysteine". International Journal of Oncology 29, no. 3 (2006): 521-529. https://doi.org/10.3892/ijo.29.3.521