title: Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms: comparison to invasive human ductal breast cancer.
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 17beta-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.
authors.affiliation: Hormonal Carcinogenesis Laboratory, Division of Etiology and Prevention of Hormonal Cancers, Kansas Cancer Institute, Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160-7417, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Papa
authors.forename: Marilyn F
authors.initials: MF
authors.lastname: Davis
authors.forename: S John
authors.initials: SJ
authors.lastname: Weroha
authors.forename: C Marcelo
authors.initials: CM
authors.lastname: Aldaz
authors.forename: Karam
authors.initials: K
authors.lastname: El-Bayoumy
authors.forename: Jodi
authors.initials: J
authors.lastname: Ballenger
authors.forename: Ossama
authors.initials: O
authors.lastname: Tawfik
authors.forename: Sara Antonia
authors.initials: SA
authors.lastname: Li
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics*; D002273:Carcinogens / Q000494:pharmacology*; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D016259:Genes, myc / Q000235:genetics / Q000502:physiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D008770:Methylnitrosourea / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011003:Ploidies; D051381:Rats; D011912:Rats, Inbred ACI; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D002273:Carcinogens; D004273:DNA, Neoplasm; D004967:Estrogens; D013739:Testosterone; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea