# NITROAROMATICS: CARCINOGENITY AND METABOLISM

> **NIH NIH R01** · INSTITUTE FOR CANCER PREVENTION · 1993 · $207,470

## Abstract

1-Nitropyrene (1-NP) is considered one of the major components found in
numerous environmental sources and is tumorigenic in mouse lung and liver,
in rat mammary glands in hamster trachea and lung.  6-Nitrochrysene (6-NC),
which is carcinogenic in newborn mouse lung and liver, is the most active
compound tested in this assay, more active than benzo[a]pyrene.  In rat
mammary glands and in newborn mouse liver and lung, multiple DNA adducts
were detected following administration of 1-NP.  In contrast one major
adduct was detected in newborn mouse liver and lung following
administration of 6-NC.  Based on our results we hypothesized that the
major metabolic activation pathway of 1-NP in newborn mice occurs via
nitroreduction and in Sprague-Dawley rats via ring oxidation; both pathways
are essential for the metabolic activation of 6-NC in newborn mice.  In
order to clearly define the biological activities of these compounds,
assess the possible risks associated with human exposure, and test our
hypothesis our aims are:  1) Elucidate the structures of the major DNA
adducts detected in newborn mouse liver and lung and in rat liver and
mammary glands following the administration of 1-NP; 2) Compare the
tumorigenic activity of 1-NP and its ring oxidized metabolites in a)
Newborn mice, b) Newborn female Sprague-Dawley rats; 3) Develop sensitive
analytical methods for detecting urinary metabolites of 1-NP in humans; 4)
Compare the tumorigenic activities of 6-NC and its metabolites derived from
nitroreduction and ring oxidation in newborn female Sprague-Dawley rats; 5)
Compare the tumorigenic activities of
1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-aminochrysene
(1,2-DHD-3,4-oxide-6-AC) and
1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysene (1,2-DHD-3,4-oxide-C) in
newborn mice; 6) Establish the relationship between the levels of DNA
adducts in newborn mouse lung and liver and the capacity for tumor
induction by 1,2-DHD-3,4-oxide-6-AC and 1,2-DHD-3,4-oxide-C.

## Key facts

- **NIH application ID:** 3173082
- **Project number:** 5R01CA035519-10
- **Recipient organization:** INSTITUTE FOR CANCER PREVENTION
- **Principal Investigator:** KARAM E EL-BAYOUMY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $207,470
- **Award type:** 5
- **Project period:** 1983-07-01 → 1994-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173082

## Citation

> US National Institutes of Health, RePORTER application 3173082, NITROAROMATICS: CARCINOGENITY AND METABOLISM (5R01CA035519-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173082. Licensed CC0.

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