Genetic toxicities of human teratogens

Abstract

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-l0% to exposure to a known x 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 Ž . 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 The information used in making these comparisons comes from the published literature as well as from unpublished data of the U.S. National Ž . Toxicology Program NTP . q 1997 Elsevier Science B.V.) Corresponding author. Tel.: q1-919-541-187; Fax: q1-919-541-4634; E-mail: bishop@niehs.nih.gov 0027-5107r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved.Ž . PII S 0 0 2 7 -5 1 0 7 9 7 0 0 1 7 3 -5 ( ) J. B. Bishop et al.r Mutation Research 396 1997 9-43 10

Detection of in vivo DNA Damage Induced by Ethanol in Multiple Organs of Pregnant Mice Using the Alkaline Single Cell Gel Electrophoresis (Comet) Assay

“…There are many studies about ethanol teratogenicity, especially about the effects of chronic alcohol consumption. Binge drinking during pregnancy is also considered as important factor of FAS, as possible human teratogen [2,13]. We administered ethanol to pregnant mice on Day 7 of gestation.…”

“…The cortical atrophy or alcoholic cerebellar atrophy are often reported in chronic alcoholic patients [6]. The large consumption of ethanol in the pregnancy causes fetal alcohol syndrome (FAS), which is characterized by growth retardation, facial anomalies such as short palpebral fissures, flat mid face, maxillary hypoplasia, and mental retardation of the newborns [2,7,10,21].…”

Evaluation of genotoxicity through micronuclei test in workers of car and battery repair garages

“…Alcoholic beverages have been described as containing mutagenic substances (Maluf and Erdtmann, 2000). Bishop et al (1997) mention that alcohol does not induce mutations in mammal cells in vitro, whereas in vivo it induces a variety of genetic effects, including sister chromatid exchange and the production of micronuclei, where the evidence, however, is limited to certain test systems or tested organisms. According to Dittberner et al (1997), alcohol use can increase the number of micronuclei.…”

Genotoxic Profile of Motor Garage Workers

“…Bishop et al (1997) mention that alcohol does not induce mutations in mammal cells in vitro, whereas in vivo it induces a variety of genetic effects, including sister chromatid exchange and the production of micronuclei, where the evidence, however, is limited to certain test systems or tested organisms. According to Dittberner et al (1997), alcohol use can increase the number of micronuclei.…”