# DRUG METABOLISM: SUSCEPTIBILITY TO DELAYED TERATOGENESIS

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1994 · $288,074

## Abstract

During the past two decades there has been a dramatic increase in the
consumption of drugs by pregnant women.  While these drugs may be
therapeutic, or at least nontoxic to the mother, they could produce
irreparable damage to the unborn child.  It has been shown that drugs
taken during pregnancy may act as teratogens producing structural
malformations in the fetus.  Many drugs can also produce more subtle
biochemical and physiological teratogenic defects in the fetus.  While
these may be "delayed" defects that are not apparent at birth or even
during childhood, they are both longterm and permanent defects.  As a
preponderance of drugs easily pass through the placental "barrier" as
well as the mammary epithelium into the milk, the developing mammal
remains susceptible to the teratogenic effects of maternally administered
drugs from conception, through fetal development, parturition and during
nursing.  Just as maternal drug consumption can threaten the health of
the unborn child, a far more insidious danger may result from the
inadvertent exposure of the perinate to a "sea" of pervasive
environmental chemicals.  Many of the chemicals in our air, water and
food supply can cause malformations, and like certain drugs, we have
proposed that they may also produce more subtle biochemical defects.  In
support of our hypothesis, we have found that peripartum exposure to
therapeutic or dietary levels of phenytoin, phenobarbital, monosodium
glutamate (MSG) and monosodium aspartate (MSA) can all produce latent,
but permanent defects in the hepatic monooxygenase system.  In some cases
the defects are "silent", and are only expressed when the system is
challenged with an inducing agent.  In future studies we propose to
examine two fundamental questions. 1) How do the teratogens induce their
defects at the time of exposure? 2) How are the latent defects expressed
in adulthood? We plan to examine these questions by a) determining the
susceptible forms of P450 and their mRNAs, b) identifying the defects in
the induction mechanisms, c) studying the role of endogenous hormones in
the induction and expression of the monooxygenase defects, and d)
investigating the ability of hormones to reverse the abnormalities.

## Key facts

- **NIH application ID:** 2197298
- **Project number:** 5R01HD016358-10
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** BERNARD Harris SHAPIRO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $288,074
- **Award type:** 5
- **Project period:** 1983-09-01 → 1997-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197298

## Citation

> US National Institutes of Health, RePORTER application 2197298, DRUG METABOLISM: SUSCEPTIBILITY TO DELAYED TERATOGENESIS (5R01HD016358-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197298. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*