# BINDING AND METABOLISM OF TOXIC AGENTS IN THE PROSTATE

> **NIH NIH R01** · KAROLINSKA INSTITUTE · 1987 · $72,891

## Abstract

Epidemiologic studies have provided evidence that a major fraction of human
cancer is due to environmental factors.  In line with this contention a
chemical etiology of prostatic cancer has been suggested.  Most mutagens
and carcinogens undergo enzymatic activation to electrophiles which bind
covalently to proteins, RNA and DNA.  The participating enzymes, e.g.
cytochrome P-450, are normally active in the metabolism of endogenous
compounds such as steroid hormones.

Knowledge about uptake and metabolism of mutagens and carcinogens in a
particular target tissue such as the prostate not only requires insights
into the function of participating enzymes, but also necessitates
information about macromolecules in the tissue that bind the xenobiotic and
thereby may cause a selective accumulation and/or transport of the compound
in the target cells.

We propose to purify, characterize and attempt to determine the
toxicological significance of macromolecules in the rat and human prostate
gland which interact with xenobiotics, particularly
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polycyclic aromatic
hydrocarbons (PAH), and metabolites of polychlorinated biphenyls (PCB).
These binding species include, respectively, the so-called TCDD receptor,
which is thought to play a role in the mechanism of induction of a certain
isozyme of cytochrome P-450, Prostatic Secretion Protein (PSP), which binds
TCDD and PAH's and may selectively concentrate these xenobiotics in the
gland, and a macromolecule which binds methyl sulphones of PCB's.

We also propose to characterize both inducible and constitutive isozymes of
cytochrome P-450 in the rat and human prostate.  The enzymes will be
purified, antibodies will be raised against them and their respective
cDNA's will be cloned.  The molecular mechanisms underlying the specific
expression of certain isozymes of cytochrome P-450 and lack of expression
of other P-450 isozymes in the prostate will be investigated at the genomic
level.

Knowledge about mechanisms involved in binding, transport and metabolism of
mutagens/carcinogens in the prostate should provide a better understanding
of the role and nature of chemical prostatic carcinogenesis in the etiology
of prostatic carcinoma.

## Key facts

- **NIH application ID:** 3179469
- **Project number:** 5R01CA040037-02
- **Recipient organization:** KAROLINSKA INSTITUTE
- **SAM.gov UEI:** ND1DSMJ54BD3
- **Principal Investigator:** JAN-AKE GUSTAFSSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $72,891
- **Award type:** 5
- **Project period:** 1986-03-07 → 1989-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179469

## Citation

> US National Institutes of Health, RePORTER application 3179469, BINDING AND METABOLISM OF TOXIC AGENTS IN THE PROSTATE (5R01CA040037-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179469. Licensed CC0.

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