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. Author manuscript; available in PMC: 2009 Aug 15.

Published in final edited form as: Toxicol Appl Pharmacol. 2008 Apr 27;231(1):77–84. doi: 10.1016/j.taap.2008.04.014

(A)Total RNA was extracted from lung tissue of CCSP/Ki-ras mice. Real-time RT-PCR was performed to detect Ki-ras expression based on average copy number. Average copy number was obtained by normalizing transgene copy number to GAPDH copy number and is expressed as copy number ± SE. *, denotes s tatistical significance with p=0.0078 as determined by ANOVA and t-test. (B) Gene dosage dependent increase in tumor multiplicity, expressed as number of tumors per mouse/total number of mice with tumors ± SE. *, denotes statistical significance with p<0.001 as determined by ANOVA and t-test. C) Pulmonary lesions in CCSP/Ki-ras mice following treatment with DOX. a) Photomicrograph of a small hyperplastic focus in the lung periphery in a mouse treated with 100 μg/ml of DOX. H and E 2X; b) Higher magnification of focal epithelial hyperplasia in the lung of a mouse treated with 100 μg/ml of DOX. The cuboidal cells are uniform, without evidence of atypia, have round deeply basophilic nuclei, abundant eosinophilic cytoplasm, and maintain normal alveolar architecture. H and E 40X; c) An adenoma in the periphery of the lung of a mouse treated with 100 μg/ml of DOX. This lesion is well circumscribed, unencapsulated, quite solid, and compresses the adjacent parenchyma. H and E 2X; d) Higher magnification of an adenoma with papillary features in the lung treated with 100 μg/ml of DOX. Connective tissue fronds are covered by one to several layers of cuboidal or columnar cells which demonstrate mild anisocytosis. Nuclei are generally deeply basophilic and cytoplasm is abundant and eosinophilic. Occasionally mitosis present (arrow). H and E 40X.

(A)Total RNA was extracted from lung tissue of CCSP/Ki-ras mice. Real-time RT-PCR was performed to detect Ki-ras expression based on average copy number. Average copy number was obtained by normalizing transgene copy number to GAPDH copy number and is expressed as copy number ± SE. *, denotes s tatistical significance with p=0.0078 as determined by ANOVA and t-test. (B) Gene dosage dependent increase in tumor multiplicity, expressed as number of tumors per mouse/total number of mice with tumors ± SE. *, denotes statistical significance with p<0.001 as determined by ANOVA and t-test. C) Pulmonary lesions in CCSP/Ki-ras mice following treatment with DOX. a) Photomicrograph of a small hyperplastic focus in the lung periphery in a mouse treated with 100 μg/ml of DOX. H and E 2X; b) Higher magnification of focal epithelial hyperplasia in the lung of a mouse treated with 100 μg/ml of DOX. The cuboidal cells are uniform, without evidence of atypia, have round deeply basophilic nuclei, abundant eosinophilic cytoplasm, and maintain normal alveolar architecture. H and E 40X; c) An adenoma in the periphery of the lung of a mouse treated with 100 μg/ml of DOX. This lesion is well circumscribed, unencapsulated, quite solid, and compresses the adjacent parenchyma. H and E 2X; d) Higher magnification of an adenoma with papillary features in the lung treated with 100 μg/ml of DOX. Connective tissue fronds are covered by one to several layers of cuboidal or columnar cells which demonstrate mild anisocytosis. Nuclei are generally deeply basophilic and cytoplasm is abundant and eosinophilic. Occasionally mitosis present (arrow). H and E 40X.