Jan 1, 1985

Cyclophosphamide teratogenesis: a review

Teratogenesis, Carcinogenesis, and Mutagenesis
Philip E Mirkes

Abstract

Cyclophosphamide (CP) is one of the best studied teratogens; it produces primarily central nervous system and skeletal anomalies in rats, mice, rabbits, monkeys, and humans. Furthermore, CP is one of the most extensively studied antineoplastic agents. Recent work using in vitro rodent embryo culture has demonstrated that CP must be bioactivated to be teratogenic. This finding extends earlier work showing that CP must be activated to achieve its antineoplastic and mutagenic effects. Activation of CP to its teratogenic, mutagenic, and antineoplastic form is mediated by microsomal cytochrome P-450 monooxygenases, which convert CP to 4-hydroxycyclophosphamide (4OHCP). In the absence of detoxification, 4OHCP spontaneously breaks down to phosphoramide mustard (PM) and acrolein (AC). PM is the CP metabolite believed to be responsible for the antineoplastic and mutagenic effects of CP, whereas AC is thought to cause the side effects associated with CP chemotherapy. Recent work has shown that the teratogenic effects of CP are mediated by both PM and AC. Although it is far from proven, available evidence supports the hypothesis that DNA is the primary target in terms of the teratogenic, mutagenic, and antineoplastic effects of CP. Althou...Continue Reading

  • References31
  • Citations94

References

  • References31
  • Citations94

Citations

Mentioned in this Paper

Embryo
Mustard antigen
Antineoplastic Agents
Cyclophosphamide
Cytochrome P450
Skeletal System
Entire Central Nervous System
Cercopithecidae
Metabolic Detoxication, Drug
Platyrrhini

About this Paper

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