# INTERACTION OF CHROMIUM WITH MITOCHONDRIA

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1987 · $123,911

## Abstract

The overall objective of this research project is to understand the
mechanism by which chromium(VI) compounds act as carcinogens.  The three
approaches we plan to use in attacking this problem are:  (1) mitochondria
will be used as a model system for studying the uptake-reduction mechanism
proposed for chromium(VI) carcinogenicity since this organelle contains
chromium(VI) reductase activity as well as DNA (mt DNA) of defined
sequence; (2) the binding of chromium to repetitive DNA sequences of
nuclear origin will be determined since nuclear DNA may differ as a target
for chromium compounds from mitochondrial DNA; and (3) carcinogenic
chromium(VI) compounds will be compared with noncarcinogenic chromium(III)
compounds with respect to chromium binding to mt DNA and repetitive DNA in
order to distinguish interactions related to the biological activity of the
chromium compounds.

We plan to test the hypothesis that reductive activation of chromium(VI)
results in specific chromium-DNA adducts at defined DNA sequences which are
preferentially attacked because of their DNA structure.  The specific aims
of the proposed research are:  (1) Compare chromium(VI) and chromium(III)
for their ability to form chromium complexes with rat mitochondrial DNA and
repetitive DNA in vivo and in tro.  The formation and repair of
chromium-DNA adducts in mt DNA and repetitive DNA fragments will be
determined after treatment with 51Cr-labeled sodium dichromate and
chromium(III) chloride.  (2) Determine the sequence specificity of chromium
interactions with mitochondrial and repetitive DNA.  The sequence
specificity and alkaline lability of the chromium-DNA adducts on mt DNA and
repetitive DNA fragments will be determined using DNA sequencing
techniques.  (3) Determine the mechanism of chromium(VI) reduction by
mitochondrial NADH-ubiquinone oxidoreductase.  Metabolism of chromium(VI)
by Complex I and isolated components will be determined.  The generation of
reactive chromium(V) and free radical species upon reduction of
chromium(VI) by these systems will be monitored by EPR spectroscopy.  (4)
Determine the ability of cis-platinum(II) to bind to rat mitochondrial and
repetitive DNA in vivo and in vitro; and (5) Determine the effect of
chromium on the replication of mt DNA and on the expression of mt genes.

## Key facts

- **NIH application ID:** 3172680
- **Project number:** 5R01CA034869-05
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** KAREN E WETTERHAHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $123,911
- **Award type:** 5
- **Project period:** 1983-06-01 → 1989-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172680

## Citation

> US National Institutes of Health, RePORTER application 3172680, INTERACTION OF CHROMIUM WITH MITOCHONDRIA (5R01CA034869-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172680. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*