Chromosomal Teratogens

Microwaves inhibit thymidine incorporation by DNA blockage in cultured cells of the Chinese hamster irradiated cells had a higher frequency of chromosome lesions (Garaj-Vrhovac et al. 1990). Microwaves induce teratogenic effects in mice when the intensity of exposure places a thermal burden on the dams and fetuses, resulting in a reduction in fetal body mass and an increased number of resorptions (O Connor 1990). 

Other adverse effects LSD is not teratogenic, but it can increase spontaneous abortions due to uterotonic effects. Use during pregnancy is unnecessary and clearly contraindicated. LSD appears to have weak, if any, mutagenic effects (Cohen and Shiloh 1977-78). Claims of chromosomal damage have showed conflicting results, and have not been supported in humans. 

Several studies have shown no evidence of mutagenicity or teratogenicity. Chromosome damage was induced in bone marrow cells of rats by intraperitoneal injection of 10-50mg/kg per day for 5 days and in peripheral blood cells of fetal lambs treated in utero with 50-250mg/%. °... 

Inhibition of spindle formation such as that caused by vincristine or colchicine stops separation of chromosomes at anaphase (see chap. 6). Proper separation of chromatids may not occur because of "stickiness 7 or bridging between the chromatids. Clearly, interference with mitosis, and hence cell proliferation, is an important cause of teratogenic effects. 

The biochemical aspects of teratology are not particularly well understood. Several kinds of biochemical mechanisms are probably involved. One such mechanism is interference with DNA synthesis, which alters the function of nucleic acids in cell replications, resulting in effects that are expressed as birth defects. Exposure to teratogenic xenobiotic substances may result in either an absence or excess of chromosomes. Enzyme inhibition (see Section 7.6) by xenobiotics can result in birth defects. Xenobiotics that deprive the fetus of essential substrates (for example, vitamins), that interfere with energy supply, or that alter the permeability of the placental membrane may all cause birth defects. 

K. Takano and M. Suzuki, Cycloxylamine, a chromosome-aberration inducing substance No teratogenicity in mice (Jpn). Congenit. Anomal. 11 51-57, 1971. 

Most common adverse effects include nausea, vomiting, diarrhea, abdominal pain, bone marrow depression with agranulocytosis, thrombocytopenia, and aplastic anemia. Cumulative toxicity is possible in elderly patients, hence it should be used cautiously. Care also should be exercised in patients with cardiac, hepatic, and renal dysfunctions. Colchicine causes teratogenicity in animals, and there are evidences of the risk of fetal chromosomal damage in humans. Colchicine should not be administered by the parenteral route as it causes severe local irritation. 

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