[Frontiers in Bioscience 2, c30-39, December 15, 1997]

	[Frontiers in Bioscience 2, c30-39, December 15, 1997] Reprints PubMed CAVEAT LECTOR
	*THE IN OVO* CARCINOGENEICITY ASSAY (IOCA): A REVIEW OF AN EXPERIMENTAL APPROACH FOR RESEARCH ON CARCINOGENESIS AND CARCINOGENICITY TESTING Harald Enzmann¹ and Klaus D. Brunnemann²** 1Bayer AG, Institute of Toxicology, 42096 Wuppertal, Germany and ²American Health Foundation, Valhalla, NY 10595, USA Received 7/21/97 Accepted 11/14/97 2. INTRODUCTION: AVIAN MODELS OF CARCINOGENICITY The use of birds in experimental cancer research is even older than the experimental induction of tumors by chemicals. Four years before the first chemical induction of an experimental tumor was described in rabbits, the viral induction of chicken sarcomas was published. Since then, the experimental induction of carcinogenesis in birds has been predominantly used for studies on viral carcinogenesis. The sensitivity of birds to chemical carcinogens became obvious with the elucidation of the turkey X disease which resulted in the discovery of the strongest known carcinogens, the aflatoxins. More recently, liver cell cancer in birds has emerged as a potential model for the synergistic effects between viral hepatitis and exposure to chemical carcinogens Bird embryos have been known to be more sensitive to viral transformation than the hatched birds. The use of bird embryos has also been suggested for tests for genotoxicity demonstrating chemically induced damage to nuclear DNA. The disadvantage of this experimental approach are the potential metabolic differences between this non-mammalian system and the rodents usually used for carcinogenicity studies. Depending on the test chemical used, activation or inactivation of the administered chemicals in the embryonic tissue may be a crucial determinant. Drug-metabolizing enzyme activities in turkey and chick liver have been shown to be similar to the activities in rat liver. In the embryonic liver, however, the activation of xenobiotics is less effective than in adult liver or at hatching. Nevertheless, measurable enzyme activities are found as early as on day 5 of development. Since the mixed function oxidase enzyme system can be induced even at this early stage, the sequential administration of an enzyme inducing agent and of the potentially carcinogenic test substance might be advantageous.

[Frontiers in Bioscience 2, c30-39, December 15, 1997]
Reprints
PubMed
CAVEAT LECTOR

THE IN OVO CARCINOGENEICITY ASSAY (IOCA): A REVIEW OF AN EXPERIMENTAL APPROACH FOR RESEARCH ON CARCINOGENESIS AND CARCINOGENICITY TESTING

Harald Enzmann¹ and Klaus D. Brunnemann²

1Bayer AG, Institute of Toxicology, 42096 Wuppertal, Germany and ²American Health Foundation, Valhalla, NY 10595, USA

Received 7/21/97 Accepted 11/14/97

2. INTRODUCTION: AVIAN MODELS OF CARCINOGENICITY

The use of birds in experimental cancer research is even older than the experimental induction of tumors by chemicals. Four years before the first chemical induction of an experimental tumor was described in rabbits, the viral induction of chicken sarcomas was published. Since then, the experimental induction of carcinogenesis in birds has been predominantly used for studies on viral carcinogenesis. The sensitivity of birds to chemical carcinogens became obvious with the elucidation of the turkey X disease which resulted in the discovery of the strongest known carcinogens, the aflatoxins.

More recently, liver cell cancer in birds has emerged as a potential model for the synergistic effects between viral hepatitis and exposure to chemical carcinogens Bird embryos have been known to be more sensitive to viral transformation than the hatched birds. The

use of bird embryos has also been suggested for tests for genotoxicity demonstrating chemically induced damage to nuclear DNA.

The disadvantage of this experimental approach are the potential metabolic differences between this non-mammalian system and the rodents usually used for carcinogenicity studies. Depending on the test chemical used, activation or inactivation of the administered chemicals in the embryonic tissue may be a crucial determinant. Drug-metabolizing enzyme activities in turkey and chick liver have been shown to be similar to the activities in rat liver. In the embryonic liver, however, the activation of xenobiotics is less effective than in adult liver or at hatching. Nevertheless, measurable enzyme activities are found as early as on day 5 of development. Since the mixed function oxidase enzyme system can be induced even at this early stage, the sequential administration of an enzyme inducing agent and of the potentially carcinogenic test substance might be advantageous.