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Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing radiation and alkylating agents

Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing... Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1–2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cdr), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-N′-nitro-N′-nitrosoguanidine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Carcinogenesis Oxford University Press

Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing radiation and alkylating agents

Carcinogenesis , Volume 10 (12) – Dec 1, 1989

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Publisher
Oxford University Press
Copyright
© Oxford University Press
ISSN
0143-3334
eISSN
1460-2180
DOI
10.1093/carcin/10.12.2279
Publisher site
See Article on Publisher Site

Abstract

Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1–2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cdr), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-N′-nitro-N′-nitrosoguanidine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals.

Journal

CarcinogenesisOxford University Press

Published: Dec 1, 1989

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