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. 1979 Apr;29:89–93. doi: 10.1289/ehp.792989

Vitamin A and the susceptibility of respiratory tract tissues to carcinogenic insult.

P Nettesheim, C Snyder, J C Kim
PMCID: PMC1637367  PMID: 510247

Abstract

The influence of vitamin A on the development of chemically induced lung carcinomas in rats was investigated. Rats were maintained on low, "normal" and excess levels of retinyl acetate (RA). Respiratory tract-squamous carcinomas were induced by intratracheal injections of 3-methylcholanthrene (3-MCA). The carcinogen doses used ranged from 1.25 to 10.0 mg of 3-MCA. Serial sacrifices conducted during the first 20 weeks following carcinogen exposure showed that metaplastic lung nodules, presumed to be precursors of later appearing carcinomas, occurred earlier and at higher incidence in rats maintained on low levels of RA than in rats maintained on moderate or high levels of RA. The development of invasive pulmonary carcinomas was enhanced at all four carcinogen doses in rats receiving low levels of RA as compared to rats receiving moderate or high levels of RA. No consistent difference in lung cancer incidence existed between the groups receiving normal and high levels of RA. The data clearly show an increased susceptibility of vitamin A-deficient rats to develop chemically induced lung cancers. Possible mechanisms underlying this effect are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bang B. G., Bang F. B. Replacement of virus-destroyed epithelium by keratinized squamous cells in vitamin A-deprived chickens. Proc Soc Exp Biol Med. 1969 Oct;132(1):50–54. doi: 10.3181/00379727-132-34146. [DOI] [PubMed] [Google Scholar]
  2. Bang F. B., Bang B. G., Foard M. Acute newcastle viral infection of the upper respiratory tract of the chicken. II. The effect of diets deficient in vitamin A on the pathogenesis of the infection. Am J Pathol. 1975 Mar;78(3):417–426. [PMC free article] [PubMed] [Google Scholar]
  3. Bang F. B., Foard M. A. The effect of acute vitamin A deficiency on the susceptibility of chicks to Newcastle disease and influenza viruses. Johns Hopkins Med J. 1971 Aug;129(2):100–109. [PubMed] [Google Scholar]
  4. Bang F. B., Foard M., Bang B. G. Acute Newcastle viral infection of the upper respiratory tract of the chicken. I. A model for the study of environmental factors on upper respiratory tract infection. Am J Pathol. 1974 Aug;76(2):333–348. [PMC free article] [PubMed] [Google Scholar]
  5. Bjelke E. Dietary vitamin A and human lung cancer. Int J Cancer. 1975 Apr 15;15(4):561–565. doi: 10.1002/ijc.2910150405. [DOI] [PubMed] [Google Scholar]
  6. Cone M. V., Nettesheim P. Effects of vitamin A on 3-methylcholanthrene-induced squamous metaplasias and early tumors in the respiratory tract of rats. J Natl Cancer Inst. 1973 Jun;50(6):1599–1606. doi: 10.1093/jnci/50.6.1599. [DOI] [PubMed] [Google Scholar]
  7. Genta V. M., Kaufman D. G., Harris C. C., Smith J. M., Sporn M. B., Saffiotti U. Vitamin A deficiency enhances binding of benzo(a)pyrene to tracheal epithelial DNA. Nature. 1974 Jan 4;247(5435):48–49. doi: 10.1038/247048a0. [DOI] [PubMed] [Google Scholar]
  8. Harris C. C., Silverman T., Smith J. M., Jackson F., Boren H. G. Proliferation of tracheal epithelial cells in normal and vitamin A-deficient Syrian golden hamsters. J Natl Cancer Inst. 1973 Sep;51(3):1059–1062. doi: 10.1093/jnci/51.3.1059. [DOI] [PubMed] [Google Scholar]
  9. Hill D. L., Shih T. W. Vitamin A compounds and analogs as inhibitors of mixed-function oxidases that metabolize carcinogenic polycyclic hydrocarbons and other compounds. Cancer Res. 1974 Mar;34(3):564–570. [PubMed] [Google Scholar]
  10. Narisawa T., Reddy B. S., Wong C. Q., Weisburger J. H. Effect of vitamin A deficiency on rat colon carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine. Cancer Res. 1976 Apr;36(4):1379–1383. [PubMed] [Google Scholar]
  11. Nettesheim P., Williams M. L. The influence of vitamin A on the susceptibility of the rat lung to 3-methylcholanthrene. Int J Cancer. 1976 Mar 15;17(3):351–357. doi: 10.1002/ijc.2910170311. [DOI] [PubMed] [Google Scholar]
  12. Rogers A. E., Herndon B. J., Newberne P. M. Induction by dimethylhydrazine of intestinal carcinoma in normal rats and rats fed high or low levels of vitamin A. Cancer Res. 1973 May;33(5):1003–1009. [PubMed] [Google Scholar]
  13. Smith D. M., Rogers A. E., Newberne P. M. Vitamin A and benzo(a)pyrene carcinogenesis in the respiratory tract of hamsters fed a semisynthetic diet. Cancer Res. 1975 Jun;35(6):1485–1488. [PubMed] [Google Scholar]
  14. Verma A. K., Boutwell R. K. Vitamin A acid (retinoic acid), a potent inhibitor of 12-O-tetradecanoyl-phorbol-13-acetate-induced ornithine decarboxylase activity in mouse epidermis. Cancer Res. 1977 Jul;37(7 Pt 1):2196–2201. [PubMed] [Google Scholar]
  15. WILHELM D. L. Regeneration of the tracheal epithelium in the vitamin-A-deficient rat. J Pathol Bacteriol. 1954 Apr;67(2):361–365. doi: 10.1002/path.1700670209. [DOI] [PubMed] [Google Scholar]

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