Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and ...

It was postulated that thalidomide causes birth defects by being metabolized to a toxic electrophilic intermediate. This hypothesis was tested by using an in vitro assay in which drug toxicity to human lymphocytes was assessed in the presence of a hepatic microsomal drug metabolizing system. Maternal hepatic microsomes from pregnant rabbits mediated the production of a metabolite that was toxic...

Early life stages are very susceptible to environmental agents; among adverse effects, teratogenesis is usually reported as the major sub lethal end point. In this contribution I will focus on the stage dependent susceptibility to physico chemical stressors evaluated by means of physical and chemical agents (e.g. UV-B irradiation, H2O2, lead, cadmium, nickel, naringenin, 2,4-D an organometalic ...

Numerous factors hinder our ability to recognize fully human teratogens. Among these are the limitations of animal and epidemiologic studies, the lack of understanding of the mechanisms of action of most teratogens, and the variability in expression of the clinical manifestation. Dose and timing of exposure, interactions with other environmental agents, and host susceptibility influence this va...

The twinning phenomenon has always interested the great public, the artists, and naturally the scientists. Isidore Geoffroy St. Hilaire has established a classification still now valid. This classification considers the different types of double monsters which are found in nature in all classes of vertebrates, including man. To explain the twinning phenomenon, the experimental realizations have...

PURPOSE Considerable information is now available concerning the risk of teratogenesis in the individual pregnancy exposed to antiepileptic drugs (AEDs). However, there is comparatively little information available concerning the risk in the subsequent pregnancies of women who continue to take the AED associated with a fetal malformation in a previous pregnancy. This article addresses this matt...

Trypan blue is known to produce embryonic abnormalities in a wide variety of animals, including rats (Gillman, Gilbert, Gillman & Spence, 1948), mice (Waddington & Carter, 1953; Hamburgh, 1954), amphibians (Waddington & Perry, 1956), chickens (Beaudoin & Wilson, 1958;Stephan & Sutter, 1961), rabbits (Ferm, 1956), and hamsters (Ferm, 1958). Studies on the teratogenic action of this dye have also...

Cytotoxic chemicals have in common the ability to act specifically on cells in cycle. Bacteria are more sensitive in the exponential growth phase than when growing slowly in media. Similar observations have been made on a variety of systems ranging from bacteria, yeast, higher plants and invertebrates to vertebrates including primates. The embryo and fetus are highly susceptible to cytotoxic ag...

Several teratogenic agents, including ionizing radiation and xenobiotics such as phenytoin, benzo[a]pyrene, thalidomide, and methamphetamine, can initiate the formation of reactive oxygen species (ROS) that oxidatively damage cellular macromolecules including DNA. Oxidative DNA damage, and particularly the most prevalent 8-oxoguanine lesion, may adversely affect development, likely via alterati...