Reciprocal paracrine interactions between normal human epithelial and mesenchymal cells protect cellular DNA from radiation-induced damage.
OBJECTIVE
To explore whether interactions between normal epithelial and mesenchymal cells can modulate the extent of radiation-induced DNA damage in one or both types of cells.


METHODS
Human primary thyrocytes (PT), diploid fibroblasts BJ, MRC-5, and WI-38, normal human mammary epithelial cells (HMEC), and endothelial human umbilical cord vein endothelial cells (HUV-EC-C), cultured either individually or in co-cultures or after conditioned medium transfer, were irradiated with 0.25 to 5 Gy of gamma-rays and assayed for the extent of DNA damage.


RESULTS
The number of gamma-H2AX foci in co-cultures of PT and BJ fibroblasts was approximately 25% lower than in individual cultures at 1 Gy in both types of cells. Reciprocal conditioned medium transfer to individual cultures before irradiation resulted in approximately a 35% reduction of the number gamma-H2AX foci at 1 Gy in both types of cells, demonstrating the role of paracrine soluble factors. The DNA-protected state of cells was achieved within 15 min after conditioned medium transfer; it was reproducible and reciprocal in several lines of epithelial cells and fibroblasts, fibroblasts, and endothelial cells but not in epithelial and endothelial cells. Unlike normal cells, human epithelial cancer cells failed to establish DNA-protected states in fibroblasts and vice versa.


CONCLUSIONS
The results imply the existence of a network of reciprocal interactions between normal epithelial and some types of mesenchymal cells mediated by soluble factors that act in a paracrine manner to protect DNA from genotoxic stress.
Nakazawa
Yuka
Y
Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Saenko
Vladimir
V
Rogounovitch
Tatiana
T
Suzuki
Keiji
K
Mitsutake
Norisato
N
Matsuse
Michiko
M
Yamashita
Shunichi
S
D002460:Cell Line; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D042783:Endothelial Cells / Q000502:physiology / Q000528:radiation effects; D004847:Epithelial Cells / Q000502:physiology / Q000528:radiation effects*; D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects*; D005720:Gamma Rays; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D001556:Hexachlorocyclohexane / Q000494:pharmacology; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D019899:Paracrine Communication / Q000502:physiology*; D013961:Thyroid Gland / Q000166:cytology; D014471:Umbilical Veins / Q000166:cytology
D017077:Culture Media, Conditioned; D001556:Hexachlorocyclohexane; D004247:DNA