Document Detail


Genetic toxicities of human teratogens.
MedLine Citation:
PMID:  9434858     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Birth defects cause a myriad of societal problems and place tremendous anguish on the affected individual and his or her family. Current estimates categorize about 3% of all newborn infants as having some form of birth defect or congenital anomaly. As more precise means of detecting subtle anomalies become available this estimate, no doubt, will increase. Even though birth defects have been observed in newborns throughout history, our knowledge about the causes and mechanisms through which these defects are manifested is limited. For example, it has been estimated that around 20% of all birth defects are due to gene mutations, 5-10% to chromosomal abnormalities, and another 5-10% to exposure to a known teratogenic agent or maternal factor [D.A. Beckman, R.L. Brent, Mechanisms of teratogenesis. Ann. Rev. Pharmacol. Toxicol. 24 (1984) 483-500; K. Nelson, L.B. Holmes Malformations due to presumed spontaneous mutations in newborn infants, N. Engl. J. Med. 320 (1989) 19-23.]. Together, these percentages account for only 30-40%, leaving the etiology of more than half of all human birth defects unexplained. It has been speculated that environmental factors account for no more than one-tenth of all congenital anomalies [D.A. Beckman, R.L. Brent, Mechanisms of teratogenesis, Ann. Rev. Pharmacol. Toxicol. 24 (1984) 483-500]. Furthermore, since there is no evidence in humans that the exposure of an individual to any mutagen measurably increases the risk of congenital anomalies in his or her offspring' [J.F. Crow, C. Denniston, Mutation in human populations, Adv. Human Genet. 14 (1985) 59-121; J.M. Friedman, J.E. Polifka, Teratogenic Effects of Drugs: A Resource for Clinicians (TERIS). The John Hopkins University Press, Baltimore, 1994], the mutagenic activity of environmental agents and drugs as a factor in teratogenesis has been given very little attention. Epigenetic activity has also been given only limited consideration as a mechanism for teratogenesis. As new molecular methods are developed for assessing processes associated with teratogenesis, especially those with a genetic or an epigenetic basis, additional environmental factors may be identified. These are especially important because they are potentially preventable. This paper examines the relationships between chemicals identified as human teratogens (agents that cause birth defects) and their mutagenic activity as evaluated in one or more of the established short-term bioassays currently used to measure such damage. Those agents lacking mutagenic activity but with published evidence that they may otherwise alter the expressions or regulate interactions of the genetic material, i.e. exhibit epigenetic activity, have likewise been identified. The information used in making these comparisons comes from the published literature as well as from unpublished data of the U.S. National Toxicology Program (NTP).
Authors:
J B Bishop; K L Witt; R A Sloane
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Mutation research     Volume:  396     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-02-03     Completed Date:  1998-02-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  9-43     Citation Subset:  IM    
Affiliation:
Laboratory of Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. bishop@niehs.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Congenital Abnormalities / etiology
DNA / drug effects,  radiation effects
DNA Damage*
Embryonic and Fetal Development / drug effects
Environmental Exposure
Female
Gene Expression Regulation / drug effects
Humans
Infant, Newborn
Infection / complications
Metabolic Diseases
Mice
Mutagenicity Tests
Pregnancy
Pregnancy Complications / metabolism
Pregnancy Complications, Infectious
Teratogens / pharmacology*,  toxicity
Chemical
Reg. No./Substance:
0/Teratogens; 9007-49-2/DNA

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