title: Prior exposure to indole-3-carbinol decreases the incidence of specific cyclophosphamide-induced developmental defects in mice.
abstract: BACKGROUND
  Indole-3-carbinol (I3C) is a product of the hydrolysis of glucobrassicin that is found in cruciferous vegetables. I3C can intervene in toxic processes that are mediated by oxidative mechanisms because it possesses the chemical and pharmacokinetic properties necessary to provide a free radical trap. Cyclophosphamide (CP) is a bifunctional alkylating agent known to produce DNA damage and to cause developmental toxicity, including malformations, in laboratory animals.
  
  
  METHODS
  Pregnant CD-1 mice were given a 100 mg/kg dose of I3C 24 or 48 hr before administration of 20 mg/kg CP on gestation day 10 (GD 10). Controls were given the vehicle (DMSO), I3C, or CP. This regimen was carried out to determine if I3C could protect against the developmental toxicity of alkylating agents, such as CP. Dams were sacrificed on GD 17 and their litters were examined for adverse effects.
  
  
  RESULTS
  Treatment with I3C 48 hr before CP administration was associated with decreased fetal limb and tail malformations. Limb malformation incidences were reduced from 42% litters affected in the CP control to 16% in the I3C/CP 48-hr treatment group, and tail malformations were reduced from 45% in the CP control to 16% in the I3C/CP 48-hr treatment group, indicating a protective effect of prior exposure to I3C. I3C given 24 hr before CP had no significant protective effect, while having an apparently adverse consequence with regard to the incidence of talipes.
  
  
  CONCLUSIONS
  Exposure of a developing mammal to indole-3-carbinol before exposure to cyclophosphamide during organogenesis can influence the teratogenicity of cyclophosphamide.
authors.affiliation: Department of Biological Sciences, The University of Alabama, Tuscaloosa, Alabama, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Bailey
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sawyer
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Behling
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Boohaker
authors.forename: Justin G
authors.initials: JG
authors.lastname: Hicks
authors.forename: Molly A
authors.initials: MA
authors.lastname: O'donnell
authors.forename: Kelli R
authors.initials: KR
authors.lastname: Stringer
authors.forename: Jane F
authors.initials: JF
authors.lastname: Rasco
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Hood
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000818:Animals; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005333:Fetus / Q000002:abnormalities* / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity; D011247:Pregnancy
chemical_list: D007211:Indoles; D009153:Mutagens; D003520:Cyclophosphamide; C016517:indole-3-carbinol