Acquired Chromosomal Anomalies Induced in Mice by Injection of a Teratogen in Pregnancy

Abstract

The experiments herein reported were undertaken to test whether a selected teratogen that can cause anomalies in 95 percent of fetuses can also cause chromosomal anomalies. 6-Amino nicotinamide was selected as the teratogenic agent, cleft palate as the deformity to be induced, and pregnant outbred females of the 15year-old Phipps mouse colony as the biologic model to be used in the experiments. This agent, this defect, and this animal were chosen because much work had been done on chemical, morphologic, and embryological aspects of all three variables (1).Pilot studies were made to establish the critical period for production of cleft palate by 6-amino nicotinamide in offspring of pregnant females of the Phipps mouse colony. Standard methods were modified and applied for the demonstration of chromosomal structure of cells of tissues adjacent to and remote from palatal defects induced by the administration of 6-amino nicotinamide to pregnant females around the 13th day of gestation. Chromosomal analyses were also carried out on maternal bone marrow, a tissue regularly in a high state of mitotic activity, to determine whether or not 6-amino nicotinamide injection had any pathogenic effect on maternal chromosomal patterns. For purposes of comparison similar studies were made of chromosomal patterns in cells of

In Vivo Effects of Vinblastine and Podophyllin on Dividing Cells of Dba Mouse Fetuses

“…Ingalls et al (1963) found a high frequency of chromosome fragmentation and polyploidy in cell cultures of tissues adjacent to cleft palate induced in mouse fetuses by 6-aminonicotinamide. Cytogenetic aberrations including mitotic irregularities and karyotype anomalies have been observed in mouse fetuses exposed to trypan blue (Joneja and Ungthavorn, 1968).…”

Salicylate‐Induced Fetal Death and Malformations in Two Mouse Strains

“…A direct effect on the cell could produce chromosomal anomalies responsible for a deformed structure, as demonstrated with 6-amino nicotinamide in cleft palate [9]. More facts have, however, been assembled concerning interference with the metabolism in the tissue of maldeveloping structures [13,141.…”

Clastogenic effects of transplacental exposure of mouse embryos to nitrogen mustard or cyclophosphamide

“…Previous cytogenetic studies have shown that transplacental exposure of rodent embryos to agents that are clastogenic in adult tissues also induces chromosomal aberrations in embryo cells [Ingalls et al, 1963;Tamboise and Tamboise, 1964;Soukup et al, 1965;Roux et al, 1971;Michelmann et al, 1975;Seiber et al, 1978;Basler et al, 19791. Although there is no direct evidence that induction of chromosomal aberrations in individual cells of developing embryos leads to clinical abnormalities, evidence from epidemiological surveys and animal studies indicates that transplacental exposure to known genotoxic agents increases the risk of fetal loss, congenital malformation, malignancy and mutations.…”