neoplasm
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• mammary tumors are observed in 2/23 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice
• in cell lines developed from individual mammary tumors from two of the conditional knockout lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line
• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line
• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases
• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay
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integument
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• mammary tumors are observed in 2/23 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice
• in cell lines developed from individual mammary tumors from two of the conditional knockout lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line
• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line
• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases
• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay
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endocrine/exocrine glands
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• mammary tumors are observed in 2/23 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice
• in cell lines developed from individual mammary tumors from two of the conditional knockout lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line
• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line
• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases
• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay
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