Gap junctions play a role in the 'bystander effect' of the herpes simplex virus thymidine kinase/ganciclovir system in vitro

A. A. Elshami; A. Saavedra; H. Zhang; J. C. Kucharczuk; D. C. Spray; G. I. Fishman; K. M. Amin; L. R. Kaiser; S. M. Albelda

Gap junctions play a role in the 'bystander effect' of the herpes simplex virus thymidine kinase/ganciclovir system in vitro

A. A. Elshami, A. Saavedra, H. Zhang, J. C. Kucharczuk, D. C. Spray, G. I. Fishman, K. M. Amin, L. R. Kaiser, S. M. Albelda

Neuroscience

Research output: Contribution to journal › Article › peer-review

257 Scopus citations

Abstract

Tumor cells transduced with the herpes simplex virus thymidine kinase (HSVtk) gene are sensitive to the anti-viral drug ganciclovir (GCV). However, nearby untransduced tumor cells are also efficiently killed. The mechanism of this 'bystander effect' was studied by comparing pairs of tumor cell lines transfected with connexin genes that differed only in their degree of gap junctional communication. More efficient cell killing was uniformly seen in connexin transfectants compared with the less coupled cell lines. These results provide direct evidence that gap junctional communication plays an important role in mediating the bystander effect of the HSVtk/GCV system in vitro and have important prognostic and therapeutic implications for future gene therapy trials.

Original language	English (US)
Pages (from-to)	85-92
Number of pages	8
Journal	Gene Therapy
Volume	3
Issue number	1
State	Published - Jan 1996

Keywords

bystander effect
ganciclovir
gap junctions
gene therapy
thymidine kinase

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics

Cite this

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title = "Gap junctions play a role in the 'bystander effect' of the herpes simplex virus thymidine kinase/ganciclovir system in vitro",

abstract = "Tumor cells transduced with the herpes simplex virus thymidine kinase (HSVtk) gene are sensitive to the anti-viral drug ganciclovir (GCV). However, nearby untransduced tumor cells are also efficiently killed. The mechanism of this 'bystander effect' was studied by comparing pairs of tumor cell lines transfected with connexin genes that differed only in their degree of gap junctional communication. More efficient cell killing was uniformly seen in connexin transfectants compared with the less coupled cell lines. These results provide direct evidence that gap junctional communication plays an important role in mediating the bystander effect of the HSVtk/GCV system in vitro and have important prognostic and therapeutic implications for future gene therapy trials.",

keywords = "bystander effect, ganciclovir, gap junctions, gene therapy, thymidine kinase",

author = "Elshami, {A. A.} and A. Saavedra and H. Zhang and Kucharczuk, {J. C.} and Spray, {D. C.} and Fishman, {G. I.} and Amin, {K. M.} and Kaiser, {L. R.} and Albelda, {S. M.}",

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AU - Elshami, A. A.

AU - Saavedra, A.

AU - Zhang, H.

AU - Kucharczuk, J. C.

AU - Spray, D. C.

AU - Fishman, G. I.

AU - Amin, K. M.

AU - Kaiser, L. R.

AU - Albelda, S. M.

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Y1 - 1996/1

N2 - Tumor cells transduced with the herpes simplex virus thymidine kinase (HSVtk) gene are sensitive to the anti-viral drug ganciclovir (GCV). However, nearby untransduced tumor cells are also efficiently killed. The mechanism of this 'bystander effect' was studied by comparing pairs of tumor cell lines transfected with connexin genes that differed only in their degree of gap junctional communication. More efficient cell killing was uniformly seen in connexin transfectants compared with the less coupled cell lines. These results provide direct evidence that gap junctional communication plays an important role in mediating the bystander effect of the HSVtk/GCV system in vitro and have important prognostic and therapeutic implications for future gene therapy trials.

AB - Tumor cells transduced with the herpes simplex virus thymidine kinase (HSVtk) gene are sensitive to the anti-viral drug ganciclovir (GCV). However, nearby untransduced tumor cells are also efficiently killed. The mechanism of this 'bystander effect' was studied by comparing pairs of tumor cell lines transfected with connexin genes that differed only in their degree of gap junctional communication. More efficient cell killing was uniformly seen in connexin transfectants compared with the less coupled cell lines. These results provide direct evidence that gap junctional communication plays an important role in mediating the bystander effect of the HSVtk/GCV system in vitro and have important prognostic and therapeutic implications for future gene therapy trials.

KW - bystander effect

KW - ganciclovir

KW - gap junctions

KW - gene therapy

KW - thymidine kinase

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Gap junctions play a role in the 'bystander effect' of the herpes simplex virus thymidine kinase/ganciclovir system in vitro

Abstract

Keywords

ASJC Scopus subject areas

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