A study of the teratogenic effects of 3,3-dimethyl-1-phenyltriazene
Abstract
The purposes of these four studies were to characterize DMPT-induced micrognathism in the rat and investigate mechanisms of the chemical's teratogenic organotropism. Pregnant rats given 30 mg DMPT/kg intraperitoneally (i.p.) on day 12 of gestation were killed at sequential time periods. Maternal toxicity (decreased maternal weight gain and food consumption) was present in DMPT-treated rats, but other maternal profiles were unaffected. Fetotoxicity (decreased fetal size and delayed ossification) was marked in treated litters. Micrognathism, CNS hypoplasia and dysplasia, and digital malformations were in 80% of exposed litters and fetuses. Micrognathism was also induced by 30 mg DMPT/kg on day 11 or 13 and 15 mg DMPT/kg on day 12, but in a much lower percentage of litters and fetuses. Ultrastructural alterations consisted of apoptosis of the neural tube and mandible. The distribution of apoptosis did not match the distribution of gross malformations. The intra-embryonic distribution of DMPT was assessed using 14C-DMPT. DMPT accumulated within the embryo, possibly due to placental biotransformation, but intra-embryonic chemical distribution did not match the distribution of gross malformations. In an effort to determine if 0-6-methylguanine was responsible for the DMPT-induced micrognathism observed in rat fetuses, hamsters, deficient in the repair enzyme for this adduct, were treated with DMPT, but doses which produced micrognathism also produced marked embryolethality.
Degree
Ph.D.
Advisors
Kazacos, Purdue University.
Subject Area
Animal diseases
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