Influence of antibiotic treatment on breast carcinoma development in proto-neu transgenic mice.
The effect of prolonged antibiotic treatments on tumor development was evaluated in proto-neu transgenic mice, which spontaneously develop mammary carcinomas. Virgin transgenic mice were treated with metronidazole/ciprofloxacin or gentamicin through the drinking water. The hazard ratio [HR; 95% confidence interval (95% CI)] of breast cancer occurrence in metronidazole/ciprofloxacin-treated mice was more than triple that for controls [3.11 (1.13-8.53); P = 0.028], whereas only a slight increase in HR (95% CI) was observed in gentamicin-treated mice [1.39 (0.56-3.47); P = 0.481]. Tumor growth rate in gentamicin-treated mice was significantly faster than in untreated control mice (P = 0.043). Moreover, mammary glands from mice treated with either antibiotic regimen showed increased lobulization, with more numerous and more developed terminal ductal lobular units than in controls. These results indicate that prolonged exposure to relevant doses of antibiotics affects the mammary glands in this particular model of HER-2/neu transgenic mice; further studies to understand the precise mechanism by which antibiotic treatments influence mammary gland differentiation are critical.
Rossini
Anna
A
Molecular Targeting Unit, Medicine Laboratory Unit, and Unit of Medical Statistics and Biometry, Department of Experimental Oncology and Laboratories, National Cancer Institute, USA.
Rumio
Cristiano
C
Sfondrini
Lucia
L
Tagliabue
Elda
E
Morelli
Daniele
D
Miceli
Rosalba
R
Mariani
Luigi
L
Palazzo
Marco
M
Ménard
Sylvie
S
Balsari
Andrea
A
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D002939:Ciprofloxacin / Q000633:toxicity; D003043:Cocarcinogenesis; D005260:Female; D018734:Genes, erbB-2; D020022:Genetic Predisposition to Disease; D005839:Gentamicins / Q000633:toxicity; D008321:Mammary Glands, Animal / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics*; D008795:Metronidazole / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats
D000890:Anti-Infective Agents; D005839:Gentamicins; D008795:Metronidazole; D002939:Ciprofloxacin