# Regulation of p53 and Checkpoint Signaling by Chromium(VI)

> **NIH NIH R01** · BROWN UNIVERSITY · 2022 · $365,625

## Abstract

Project Summary
Hexavalent chromium [Cr(VI)] is firmly established as a human carcinogen by epidemiological studies
in occupationally exposed groups from different countries. The presence of this toxic metal at
numerous Superfund sites and in drinking water across many states has also raised significant public
health concerns regarding cancer and other health risks associated with environmental exposures to
Cr(VI). Ingestion of Cr(VI) through drinking water produced clear evidence of carcinogenicity in the
small intestine of mice. The low-dose extrapolation of these animal data to environmental risks in
humans requires knowledge of the mechanism of the carcinogenic action for Cr(VI), which dictates
the use of specific extrapolation models. Cr(VI) generates Cr-DNA adducts as the most abundant
form of DNA damage but these adducts are weakly duplex-distorting and do not induce classic DNA
damage responses. This project will investigate a hypothesis on a major role of DNA repair products
of the initially formed Cr-DNA damage in the activation of noncanonical branches of genotoxic stress
signaling. We will also examine the biochemical processes governing the responsiveness of the
stress-sensitive transcription factor p53 and a protective G1 checkpoint to Cr-DNA damage. The
completion of this work is expected to provide mechanistic explanations for unusual genetic features
of Cr(VI)-induced lung tumors and improve human risk assessment.

## Key facts

- **NIH application ID:** 10306386
- **Project number:** 5R01ES028072-05
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Anatoly Zhitkovich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $365,625
- **Award type:** 5
- **Project period:** 2017-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10306386

## Citation

> US National Institutes of Health, RePORTER application 10306386, Regulation of p53 and Checkpoint Signaling by Chromium(VI) (5R01ES028072-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10306386. Licensed CC0.

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