Aroclor-1254 affects mRNA polyadenylation, translational activation, cell morphology, and DNA integrity of rat primary prostate cells.
Environmental xenobiotics have been shown to act as endocrine disruptors and to be implicated in increased cancer susceptibility. In particular, there is a significant concern regarding the impact of these contaminants on prostate cancer development and progression. However, the mechanisms with which these contaminants exert their detrimental effects are yet unclear and need to be further elucidated. In the present study, we investigated the effects of Aroclor-1254, a mixture of more than 60 environmental pollutants belonging to the polychlorinated biphenyl family, on rat prostate primary cultures. The results obtained after 24-h exposure indicated the ability of this contaminant mixture to influence mRNA stability and length of the 3'-end poly(A)tail of Connexin-32, Connexin-43, and heat shock protein-70. Consistent with this observation, immunostaining experiments demonstrated the altered availability of the encoded proteins. We also focused our attention on possible effects of Aroclor-1254 on cell morphology and could detect ultrastructural changes with gap junction disruption, fusion of single cells into clusters, and different aspects of apoptosis that became evident when exposure to Aroclor-1254 was extended to 72 h. The effects on the nuclear compartment were confirmed by the results obtained with Comet assay that showed DNA decompression and double-strand breaks already after 24-h exposure. Taken together, these findings show a detrimental effect of Aroclor 1254 on rat prostate cells and indicate a possible association between exposure to polychlorinated biphenyl mixture and induction of transformation process in prostate cells.
Cillo
Fabiana
F
Laboratory of Biomedical Embriology, School of Veterinary Medicine, UniStem, University of Milan, Milan, Italy. fabiana.cillo@unimi.it
de Eguileor
Magda
M
Gandolfi
Fulvio
F
Brevini
Tiziana A L
TA
D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D018031:Connexin 43 / Q000235:genetics; D017630:Connexins / Q000235:genetics; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004785:Environmental Pollutants / Q000633:toxicity*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D008297:Male; D026723:Polyadenylation / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000648:ultrastructure; D014176:Protein Biosynthesis / Q000187:drug effects*; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D015854:Up-Regulation; D000097002:Gap Junction beta-1 Protein
D020111:Chlorodiphenyl (54% Chlorine); D018031:Connexin 43; D017630:Connexins; D004247:DNA; D004785:Environmental Pollutants; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein