Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms: Comparison to invasive human ductal breast cancer

Jonathan J. Li, Dan Papa, Marilyn F. Davis, S. John Weroha, C. Marcelo Aldaz, Karam El-Bayoumy, Jodi Ballenger, Ossama Tawfik, Sara Antonia Li

Research output: Contribution to journalArticle

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Abstract

To ascertain differences between solely hormone- and chemical carcinogen-induced murine mammary gland tumors (MGTs), a direct comparison of their ploidy status was assessed. Nuclear image cytometry (NIC) was used to evaluate ploidy in ductal carcinoma in situ (DCIS) and MGTs induced solely by 17β-estradiol (E 2 ) in female A-strain Copenhagen Irish hooded gene rats (ACI) and E 2 plus testosterone propionate in male Noble rats. These results were compared to ploidy data from primary MGTs induced by two synthetic carcinogens, 7,12-dimethylbenz[a]antracene and nitrosomethylurea in female Brown Lewis Norway rats and an environmental carcinogen, 6-nitrochrysene, in female Sprague-Dawley rats. Both DCIS and primary MGTs induced solely by hormones were highly aneuploid (>84%), whereas MGTs induced by either synthetic or environmental carcinogens were primarily diploid (>85%). Examination of 76 metaphase plates obtained from eight individual E 2 -induced ACI female rat MGTs revealed the following consistent chromosome alterations: gains in chromosomes 7, 11, 12, 13, 19, and 20 and loss of chromosome 12. On Southern blot analysis, six of nine ACI female rat primary E 2 -induced MGTs (66%) exhibited amplified copy numbers (range: 3.4-6.9 copies) of the c-myc gene. Fluorescence in situ hybridization (FISH) analysis of these MGTs revealed specific fluorescent hybridization signals for c-myc (7q33) on all three homologs of a trisomy in chromosome 7. NIC analysis of 140 successive nonfamilial sporadic invasive human ductal breast cancers (BCs) showed an aneuploid frequency of 61%, while 31 DCISs revealed a 71% aneuploid frequency. These results clearly demonstrate that the female ACI rat E 2 -induced MGTs more closely resemble invasive human DCIS and ductal BC in two pertinent aspects: they are highly aneuploid compared with chemical carcinogen-induced MGTs and exhibit a high frequency of c-myc amplification.

Original languageEnglish (US)
Pages (from-to)56-65
Number of pages10
JournalMolecular Carcinogenesis
Volume33
Issue number1
DOIs
StatePublished - Jan 21 2002

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Animal Mammary Neoplasms
Ploidies
Carcinogens
Human Mammary Glands
Hormones
Breast Neoplasms
Inbred ACI Rats
Carcinoma, Intraductal, Noninfiltrating
Aneuploidy
Image Cytometry
Environmental Carcinogens
Chromosomes, Human, Pair 7
Carcinoma, Ductal, Breast
Testosterone Propionate
Methylnitrosourea
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 11
myc Genes
Trisomy
Metaphase

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Li, Jonathan J. ; Papa, Dan ; Davis, Marilyn F. ; Weroha, S. John ; Aldaz, C. Marcelo ; El-Bayoumy, Karam ; Ballenger, Jodi ; Tawfik, Ossama ; Li, Sara Antonia. / Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms : Comparison to invasive human ductal breast cancer. In: Molecular Carcinogenesis. 2002 ; Vol. 33, No. 1. pp. 56-65.
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Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms : Comparison to invasive human ductal breast cancer. / Li, Jonathan J.; Papa, Dan; Davis, Marilyn F.; Weroha, S. John; Aldaz, C. Marcelo; El-Bayoumy, Karam; Ballenger, Jodi; Tawfik, Ossama; Li, Sara Antonia.

In: Molecular Carcinogenesis, Vol. 33, No. 1, 21.01.2002, p. 56-65.

Research output: Contribution to journalArticle

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T1 - Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms

T2 - Comparison to invasive human ductal breast cancer

AU - Li, Jonathan J.

AU - Papa, Dan

AU - Davis, Marilyn F.

AU - Weroha, S. John

AU - Aldaz, C. Marcelo

AU - El-Bayoumy, Karam

AU - Ballenger, Jodi

AU - Tawfik, Ossama

AU - Li, Sara Antonia

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N2 - To ascertain differences between solely hormone- and chemical carcinogen-induced murine mammary gland tumors (MGTs), a direct comparison of their ploidy status was assessed. Nuclear image cytometry (NIC) was used to evaluate ploidy in ductal carcinoma in situ (DCIS) and MGTs induced solely by 17β-estradiol (E 2 ) in female A-strain Copenhagen Irish hooded gene rats (ACI) and E 2 plus testosterone propionate in male Noble rats. These results were compared to ploidy data from primary MGTs induced by two synthetic carcinogens, 7,12-dimethylbenz[a]antracene and nitrosomethylurea in female Brown Lewis Norway rats and an environmental carcinogen, 6-nitrochrysene, in female Sprague-Dawley rats. Both DCIS and primary MGTs induced solely by hormones were highly aneuploid (>84%), whereas MGTs induced by either synthetic or environmental carcinogens were primarily diploid (>85%). Examination of 76 metaphase plates obtained from eight individual E 2 -induced ACI female rat MGTs revealed the following consistent chromosome alterations: gains in chromosomes 7, 11, 12, 13, 19, and 20 and loss of chromosome 12. On Southern blot analysis, six of nine ACI female rat primary E 2 -induced MGTs (66%) exhibited amplified copy numbers (range: 3.4-6.9 copies) of the c-myc gene. Fluorescence in situ hybridization (FISH) analysis of these MGTs revealed specific fluorescent hybridization signals for c-myc (7q33) on all three homologs of a trisomy in chromosome 7. NIC analysis of 140 successive nonfamilial sporadic invasive human ductal breast cancers (BCs) showed an aneuploid frequency of 61%, while 31 DCISs revealed a 71% aneuploid frequency. These results clearly demonstrate that the female ACI rat E 2 -induced MGTs more closely resemble invasive human DCIS and ductal BC in two pertinent aspects: they are highly aneuploid compared with chemical carcinogen-induced MGTs and exhibit a high frequency of c-myc amplification.

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