# DEVELOPMENTAL TOXICITY OF RETINOIDS AND MODE OF ACTION

> **NIH NIH R37** · THOMAS JEFFERSON UNIVERSITY · 1994 · $176,222

## Abstract

After the discovery that the two vitamin A related drugs - Accutane
(registered trademark) and Tigason (registered trademark) - are
human teratogens, the question has arisen if vitamin A (retinol)
itself is also teratogenic if ingested as an oral supplement.
Information gathered until the year 1986 from at least seven
published and eleven unpublished case reports indicate the
occurrence of major malformations in infants if daily intake of
vitamin A during pregnancy was 25,000 IU or more.  There are no
epidemiological studies to provide corroborative data, but several
good animal models are available.  Our aim is to understand the
biological basis (i.e., mechanism) of vitamin A-induced
teratogenicity in an animal model (mouse) by studying the
underlying cellular and subcellular events in susceptible and
embryonic tissues.  Previous studies under this project have
provided evidence that a) formation of retinoic acid from retinol
is the first step in this mechanism and that b) there are certain
specific structural requirements in the retinoid molecule that
enhance or lower its teratogenic activity.

Our specific aims are first to attempt an identification of the
likeliest active natural metabolite or metabolites of
retinol/retinoic acid by means of whole animal and tissue culture
bioassays established previously.  Radiochemical and HPLC
methodologies will be used in this attempt, and synthetic retinoid
compounds will be included in the analyses.  Second, select
variably-active retinoids from ongoing studies and use them to
compare their ability to localize and interact with cellular and
nuclear components in the embryonic target tissues.  Cell
fractionation, density gradient centrifugation, SDS/polyacrylamide
gel electrophoresis, and HPLC will supplement other methods to seek
the role of nuclear retinoid receptor(s) in vitamin A-induced
teratogenic response.  This research will bring us closer to a
proposal that the physiologic and pharmacologic effects of vitamin
A have a common basis.

## Key facts

- **NIH application ID:** 2198117
- **Project number:** 5R37HD020925-09
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** DEVENDRA M KOCHHAR
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $176,222
- **Award type:** 5
- **Project period:** 1985-12-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198117

## Citation

> US National Institutes of Health, RePORTER application 2198117, DEVELOPMENTAL TOXICITY OF RETINOIDS AND MODE OF ACTION (5R37HD020925-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198117. Licensed CC0.

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