CARCINOGENESIS IN METALLOTHIONEIN-DEFICIENT MICE

Project: Research project

Project Details

Description

Metallothionein (MTs) are a group of small cysteine-rich proteins that
bind heavy metals with high affinity. It is widely held that MTs
function to protect cells/organisms form heavy metal toxicity because of
their binding affinity for heavy metals and because expression of MT
genes is induced by heavy metals. In addition to their widely accepted
role in preventing heavy metal toxicity, evidence indicates that the MTs
may be involved in protection from the carcinogenic action of various
chemicals/compounds. For example, transfected cells that overexpress MT
show increase resistance to the toxicity of alkylating agents which are
known to induce cancer in rodents. In addition, studies with rats
suggest that tissues that do not express MT are susceptible to d-induced
carcinogenesis. The overall strategy described in this application is designed to
directly test the hypothesis that MT protects an organism from the
carcinogenic effects of alkylating agents and Cd. The specific aims of
the project are: 1) to produce and characterize mice lacking a functional
mMT-I gene, mMT-II gene, and mMT-I and mMT-II (mMT-I/mMT-II) genes, 2)
to determine if low tissue levels of MT are correlated to an increased
incidence of carcinogenesis induced by alkylating agents, 3) to determine
if low tissue levels of MT are correlated with an increase incidence of
carcinogenesis induced by Cd.
StatusFinished
Effective start/end date12/15/9311/30/97

Funding

  • National Institutes of Health: $121,536.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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