Effect of tumor-promoting and anti-promoting chemicals on the viability and junctional coupling of human HeLa cells transfected with DNAs coding for various murine connexin proteins.
Gap-junctional intercellular communication is thought to be essential for maintaining cellular homeostasis and growth control. Its perturbation entails toxicological implications and it has been correlated with the in vivo tumor-promoting potential of chemicals. Little is known about the mechanism(s) responsible for the tumor promoters interference with the cellular coupling. Moreover, nongenotoxic carcinogens, as well as connexins (gap-junctional protein subunits), are known to be organ-/tissue-specific; this implies that the effect of different agents should be evaluated on their specific target, that is, connexin. To investigate the role of different connexins in regulating gap-junctional gating and to compare the properties of homotypic junctional channels, we evaluated the effects of tissue-specific tumor promoters and anti-promoters on the viability and intercellular coupling (dye-transfer) of HeLa cells stably transfected with cDNAs coding for connexin(cx)43, cx40, cx26 and cx32. The results demonstrate that the transfectants possess individual junctional permeabilities, differentially affected by the chemicals, they also show different sensitivities to the cytotoxic effect of the compounds. These findings confirm that connexin diversity may be responsible for the different gating properties of gap-junctional channels, being also suggestive for their separate functions and independent regulatory mechanisms.
Mazzoleni
G
G
Unit of General Pathology and Immunology, School of Medicine, University of Brescia, Italy.
Camplani
A
A
Telo
P
P
Pozzi
A
A
Tanganelli
S
S
Elfgang
C
C
Willecke
K
K
Ragnotti
G
G
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D017629:Gap Junctions / Q000187:drug effects; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry; D051379:Mice; D014162:Transfection
D002273:Carcinogens; D017630:Connexins; D005456:Fluorescent Dyes; C000607042:GJB2 protein, human; D007546:Isoquinolines; D000072259:Connexin 26; D004247:DNA; C017475:lucifer yellow