title: In vivo long-term effects of retinoic acid exposure in utero on induced tumours in adult mouse skin.
abstract: BACKGROUND
  Retinoic acid (RA) and its analogues (retinoids) are promising agents in skin cancer prevention following either topical application or oral administration. However, long-term in vivo effects of RA on chemically induced hyperplastic epidermal foci in adult mouse skin have also been described, casting some doubt with regard to its chemopreventive activity.
  
  
  OBJECTIVE
  To characterize chemically induced skin tumours and to investigate the in vivo long-term action and preventive effect of RA on adult mouse skin carcinogenesis.
  
  
  METHODS
  Fifty-six adult Naval Medical Research Institute mice, exposed (n = 28) or not exposed (n = 28) to RA in utero.
  
  
  METHODS
  Mice were treated with a standard two-stage skin carcinogenesis protocol, which included an initiating application of 7,12-dimethylbenz(a)anthracene followed by promotion with 12-O-tetradecanoylphorbol 13-acetate.
  
  
  RESULTS
  Retinoic acid administered to pregnant mice showed a long-term inhibitory action on cell differentiation and development of chemically induced tumours on the adult skin of their offspring, as well as a stimulatory effect on cell proliferation and expression of an early marker of malignant progression (keratin 13).
  
  
  CONCLUSIONS
  The results suggest that RA exposure in utero confers long-lasting effects on adult mouse skin carcinogenesis. These include chemopreventive activity (reduced number of tumours), as well as enhancement of squamous papilloma progression, which appears to be due to enhanced keratinocyte proliferation and suppression of epidermal maturation. The clinical significance of these findings is not known for other routes of RA administration at this time.
authors.affiliation: Animal Medicine and Surgery Department, Faculty of Veterinary Science, Complutense University of Madrid (UCM), Puerta de Hierro s/n, Madrid, 28040, Spain.
authors.forename: Rosa A
authors.initials: RA
authors.lastname: García-Fernández
authors.forename: Claudia
authors.initials: C
authors.lastname: Pérez-Martínez
authors.forename: Maria J
authors.initials: MJ
authors.lastname: García-Iglesias
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D007636:Keratoacanthoma / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control*; D011247:Pregnancy; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate