# INDUCTION OF GENE EXPRESSION BY CHEMICAL CARCINOGENS

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 1993 · $145,061

## Abstract

A large variety of environmental pollutants are known to be toxic and/or
carcinogenic. It is therefore important to understand how organisms
respond to these xenobiotics at the cellular and molecular levels. A major
element in the detoxification of these substances is the induction of both
the cytochromes P45O1A1 and 1A2, as well as a variety of additional
proteins, which serve to oxidize these nonpolar compounds. Paradoxically,
instead of converting some of these pollutants to harmless forms, these
proteins can often activate their carcinogenic potential.

The goal of this proposal is to determine the molecular basis of the
regulation of a set of genes which is induced by polycyclic hydrocarbons
in mice. First, we plan to continue our work defining the novel post-
transcriptional mechanism of induction of the P4501A2 gene. We have
already shown that the gene is induced at the level of nuclear mRNA
processing in a hydrocarbon receptor-dependent manner. While regulation of
nuclear processing has been postulated for many years, there is no direct
evidence to date that such regulation is used for any specific gene. The
cytochrome P4501A2 gene may allow the identification and characterization
of the cis- and trans- elements that are required for hydrocarbon-
dependent post-transcriptional regulation. Second, we plan to apply the
recently developed technology of normalized cDNA libraries, to identify a
larger set of carcinogen-inducible genes, and to identify their level of
regulation. Specifically, we will construct normalized cDNA libraries
corresponding to mRNA expressed in hydrocarbon treated mouse liver, and we
will screen the libraries using a combination of subtractive hybridization
methods and direct plus-minus screening techniques. This approach will
permit the identification of relatively low abundance inducible genes over
the background of abundant liver-specific and cytochrome P450 clones.
Straightforward analysis by northern hybridization and nuclear run-on
transcription will permit an assessment of the levels of gene control
operating on each gene. By comparing a set of genes which respond to the
same hydrocarbon inducer, it will be possible to better understand the
diversity of-mechanisms controlling hydrocarbon gene control.

## Key facts

- **NIH application ID:** 3178670
- **Project number:** 2R01CA039553-09
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Kenneth S Krauter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $145,061
- **Award type:** 2
- **Project period:** 1985-04-01 → 1996-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178670

## Citation

> US National Institutes of Health, RePORTER application 3178670, INDUCTION OF GENE EXPRESSION BY CHEMICAL CARCINOGENS (2R01CA039553-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178670. Licensed CC0.

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