# MECHANISMS OF ANTICARCINOGENESIS BY DITHIOLTHIONES

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1991 · $322,791

## 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 modes of protection afforded by dietary 1, 2-
dithiole-3-thiones, reported constituents of cruciferous
vegetables, on aflatoxin Beta 1 hepatocarcinogenesis in the rat.
Previous studies from our laboratories have demonstrated that
dietary antioxidants, including 1, 2-dithiole-3-thiones, block
chemical carcinogenesis at this target site.
Evidence to date suggests that dietary antioxidants induce the
activities of carcinogen detoxication enzymes to result in lower
levels of  DNA adduct formation and enhanced carcinogen
elimination.  The proposed will extend these studies by 1)
synthesizing a series of rationally-designed analogues of 1, 2-
dithiole-3-thione; 2)evaluating the spectrum of actions and
mechanisms of these compounds on the induction of Phase I and II
enzymes and reduction in carcinogen-DNA adducts; 3) examining the
chemoprotective actions of the newly synthesized dithiolthiones as
inhibitors of gamma glutamyltranspeptidase positive lesions, a
short-term model for aflatoxin carcinogenesis, as well as hepatic
cancers; and, 4) utilizing the dithiolthione/aflatoxin
chemoprotection model to develop and validate biomarkers for
assessing both risk from carcinogen exposure and the efficacy of
anticarcinogen intervention.  The long term goal of this work is
to facilitate our understanding of how dietary constituents may
modulate the target organ risk in human populations exposed to
naturally-occurring carcinogens.

## Key facts

- **NIH application ID:** 3178348
- **Project number:** 5R01CA039416-06
- **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:** 1991
- **Award amount:** $322,791
- **Award type:** 5
- **Project period:** 1985-09-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178348

## Citation

> US National Institutes of Health, RePORTER application 3178348, MECHANISMS OF ANTICARCINOGENESIS BY DITHIOLTHIONES (5R01CA039416-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3178348. Licensed CC0.

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