# MODULATION OF AFLATOXIN TOXICITY BY DIETARY ANTIOXIDANTS

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1987 · $140,830

## Abstract

Strategies for cancer prevention involving reduction or elimination of
human exposure to environmental carcinogens may not always be possible.
Inhibition of the development of cancer by the administration of chemicals
may offer a practical alternative for reducing human cancer burden.
However, the successful utilization of chemoprotective interventions will
require solid mechanistic understanding of the action of these agents.  The
proposed study will investigate the mode of protective actions of dietary
antioxidants (butylated hydroxytoluene, butylated hydroxyanisole and
ethoxyquin) and dithiothiones, natural antioxidants found in cruciferous
vegetables on aflatoxin B1 carcinogenesis.  Dietary exposure of aflatoxin
B1, a product of mold-related spoilage of foods, has been positively
correlated with high incidences of human liver cancer in a number of
underdeveloped areas of the world.  This toxin is capable of covalent
binding to biomolecules, especially DNA and these macromolecular adducts
may pose both short and long term health risks from the resulting genotoxic
lesions in people exposed to this carcinogen.  Preliminary studies in our
laboratories have demonstrated that a number of dietary antioxidants,
including butylated hydroxytoluene, ethoxyquin and a dithiothione
(oltipraz) lower the levels of DNA adduct formation by aflatoxin B1 three
to seven fold when compared to control levels in rat liver following
exposure in vivo.  While these experiments suggest that these dietary
anti-oxidants modify xenobiotic metabolizing enzymes to result in lower
levels of total adduct formation, these antioxidants may also affect the
kinetics of removal of these adducts from DNA in the initial 48 hours
following dosage in vivo.  Therefore, we specifically propose to examine
the effects of dietary antioxidants on:  a) the quantitative and
qualitative patterns, organ specificity and repair of aflatoxin-DNA adduct
formation and removal; b) the enzymological changes related to aflatoxin
activation and detoxification and the kinetics of aflatoxin elimination;
and c) the induction of gamma-glutamyltranspeptidase positive lesions, a
short-term in vivo model for aflatoxin carcinogenesis.  These studies
should lead to a better understanding of antioxidant mechanisms for the
inhibition of carcinogenesis and to facilitate insights into how dietary
constituents may modulate the exposure status of populations to
environmentally occurring carcinogens.

## Key facts

- **NIH application ID:** 3178346
- **Project number:** 5R01CA039416-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** THOMAS W KENSLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $140,830
- **Award type:** 5
- **Project period:** 1985-09-01 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178346

## Citation

> US National Institutes of Health, RePORTER application 3178346, MODULATION OF AFLATOXIN TOXICITY BY DIETARY ANTIOXIDANTS (5R01CA039416-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178346. Licensed CC0.

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