Assessment of histopathological changes induced by drug treatment in <i>Brca1</i>-wild type and -deficient tumor lines.

<p>A, An example of histology and IHC of <i>TgK18G_T121^tg/+/Brca1^Δ/Δ/p53^Δ/Δ</i> tumors treated with cisplatin and/or olaparib (a–l). Tumor line 39877 was sensitive to drug treatment, which resulted in decreased proliferation (Ki67) (A e–h) and increased DNA damage (γ-H2AX) (A i–l). Olaparib treatment resulted in increased nuclear size and pleiomorphism (A, b, f, j) as well as decreased degree of papillary differentiation. Note the marked increase in tumor multinucleated giant cells in the cisplatin (A, c, g, k) and combination treated (A, d, h, l). Scale bar represents 100 µm. Quantitative analysis of Ki67 (B), and γH2AX (C) in 3 different tumor lines. Proliferation rate is expressed as the percentage of Ki67 positive nuclei (brown-DAB) to the total number of nuclei in the tumor section (brown-DAB + blue-hematoxylin counter-stained negative nuclei). γH2AX is expressed as the percentage of total nuclear area (blue-hematoxylin counter-stain) to the total area positive for γH2AX (brown-DAB). Statistical differences between groups were analyzed by one-way ANOVA and Tukey's multiple comparisons test. Each point represents one animal. V; vehicle, O; olaparib, C; cisplatin, O+C; olaparib and cisplatin.