Effect of selective ablation of proliferating mammary epithelial cells on MNU induced rat mammary tumorigenesis.
Proliferating cells within the terminal end buds of the virgin female rat mammary gland are the most susceptible to chemical carcinogen induced tumorigenesis. We hypothesized that selective ablation of proliferating cells in the mammary gland would reduce mammary tumor incidence upon carcinogen challenge. Selective ablation of proliferating cells was achieved by intraductal injections of Adv-RSV-tk and gancyclovir administration. Despite efficient viral transduction of the thymidine kinase protein and the apparent elimination of >90% of the proliferating cells, the rats exhibited a higher incidence of MNU induced mammary tumors arising with shorter latency as compared to control animals. Several possible explanations of the puzzling relationship between elimination of cycling cells and increased tumor incidence are discussed and alternative strategies for the prevention of breast cancer are proposed.
Sivaraman
Lakshmi
L
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Gay
Jason
J
Hilsenbeck
Susan G
SG
Shine
H David
HD
Conneely
Orla M
OM
Medina
Daniel
D
O'Malley
Bert W
BW
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D007124:Immunoenzyme Techniques; D015994:Incidence; D015552:Injections, Intralesional; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000453:epidemiology; D008770:Methylnitrosourea / Q000633:toxicity; D051381:Rats; D011920:Rats, Inbred WF; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D000998:Antiviral Agents; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir