Research Paper Volume 9, Issue 3 pp 665—686

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

Figure 1. Effect of dose on the frequency of centrosome aberrations. Fifteen HMEC strains derived from individuals of various ages were exposed to a low dose (LD) and high dose (HD) of two types of radiation namely Cs and Ti ions. Roughly equitoxic doses of Cs and Ti were used for exposures (LD-CS = 0.12 Gy; HD-CS = 0.8 Gy; LD-Ti = 0.05 Gy; HD-Ti = 0.5 Gy). Aberrant numbers of centrosomes per cell were visualized by indirect immunofluorescence microscopy using an anti-pericentrin antibody (A). Staining was carried out within days of fixation, and the number of cells containing aberrant numbers of centrosomes was counted in random regions of the slide. The majority of the cells in irradiated and unirradiated samples show one or two pericentrin foci (A: a, b). Cells with supernumerary centrosomes showed numbers of centrosomes ranging between 3 to as many as 7, and were scored as aberrant (>3P) (A: c, d). Cells were processed 9 days post-exposure and the percentage of aberrant cells in each strain was plotted relative to the unexposed population (B). Data are based on four independent experiments for high dose and two independent experiments for low dose. The frequency of cells with supernumerary (>3P) centrosomes was graphed against age of the individual from which the strain was derived (C-F). Regression analysis was used to model the relationship. The effects of lesion complexity on this relationship at a low (C) and high dose (D) were graphed. The effect of dose for Cs (E) and Ti ion exposure (F) were also graphed. Averaged data and the regression line for Cs and Ti ion exposed samples is shown with blue and red, symbols and lines respectively. In Fig. 1E and 1F, LD and HD are distinguished using dotted and full lines, respectively.