Colchicine teratogenicity

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. 

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. 

TUB [antimitotic, carcinogen, disrupts MT assembly, irritant, irritant, teratogen] Colchicine used for treating gout (joint uric acid accumulation)... 

Colchicine has been shown to be teratogenic in mice and hamsters. 

As embryogenesis involves extensive cellular proliferation, any interference with this process is potentially teratogenic. Interference with spindle formation, inhibition or arrest of DNA synthesis or the incorrect separation of chromatids all fall into this category. Inhibition of DNA synthesis, such as that caused by cytosine arabinoside, slows or arrests mitosis, which cannot progress beyond the S-phase. Thus those areas of the embryo which show extensive cellular proliferation are the most susceptible to both necrosis and subsequent malformation from cytotoxic compounds such as cytosine arabinoside. Inhibition of spindle formation such as that caused by vincristine or colchicine stops separation of chromosomes at anaphase (see page 240). Proper separation of chromatids may not occur because of stickiness or bridging between the chromatids. Clearly interference with mitosis, and hence cell proliferation, is an important cause of teratogenic effects. 

Colchicine solution at 10,000 ppm concentration caused severe irritation when applied repeatedly to rabbits eyes. Colchicine produced teratogenic effects in test animals. It caused fetal death, cytological changes, and developmental abnormalities in hamsters, rabbits, domestic animals, and mice. It tested positive to in vitro mammalian nonhuman micronucleus and... 

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