[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 *6. PERSPECTIVE OF THE IN OVO* MODEL OF CARCINOGENESIS** In ovo experiments may fill the gap between experiments with whole animals and cell culture systems, combining some advantages of both approaches. These advantages are summarized below: The IOCA is rapid, since focal and nodular preneoplastic liver lesions can be induced in 24 days and damage to mitochondrial DNA in 4 days. 1. The IOCA is less expensive than whole animal experiments. Since the experiments are terminated several days before hatching and fertilized eggs are commercially available, facilities for animal housing are not required. 2. The IOCA is logistically simple: It does not require highly sophisticated methods or expensive equipment since routine histology is sufficient for the detection of the induced nuclear alterations and focal hepatic lesions. 3. Quantification of the induced effects can be easily achieved by simple morphometric methods both for the nuclear enlargement and for the occurrence of focal hepatic lesions. 4. Proliferation-mediated effects on carcinogenesis are unlikely to affect the induction of foci in the IOCA. Similar to the partial hepatectomy in the Ito-model, the rapid growth of the embryonic liver provides such a high cell proliferation that a stimulating effect of the test substance is of little or no effect. Therefore, merely cytotoxic effects are less likely to mimic carcinogenicity. 5. The pronounced proliferation of the embryonic tissue also contributes to the high sensitivity of the assay. The induction of regenerative proliferation in potential target tissues frequently introduced in animal experiments (36, 39) is not necessary in ovo due to the high proliferation rate of the embryonic tissue. 6. An additional non-rodent species strengthens the extrapolation of animal studies to humans. 7. Finally, there is less potential of human exposure during the experiment: There is no excretion of the injected carcinogens from the eggs. The egg shell may be regarded as a barrier, at least, for the non-volatile chemicals. The amounts of the carcinogenic chemicals that are needed for the IOCA are relatively small as compared to animal experiments. It may be possible to study carcinogenic effects of chemicals in tissues other than the liver by the IOCA. However, the liver has been the favorite target organ studied in chemically-induced carcinogenesis (17). As more experience with different chemicals and different target tissues is gained the IOCA may become an increasingly valuable tool both for toxicologic carcinogenicity testing and for research on the mechanisms of chemical carcinogenesis.

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

6. PERSPECTIVE OF THE IN OVO MODEL OF CARCINOGENESIS

In ovo experiments may fill the gap between experiments with whole animals and cell culture systems, combining some advantages of both approaches. These advantages are summarized below: The IOCA is rapid, since focal and nodular preneoplastic liver lesions can be induced in 24 days and damage to mitochondrial DNA in 4 days. 1. The IOCA is less expensive than whole animal experiments. Since the experiments are terminated several days before hatching and fertilized eggs are commercially available, facilities for animal housing are not required. 2. The IOCA is logistically simple: It does not require highly sophisticated methods or expensive equipment since routine histology is sufficient for the detection of the induced nuclear alterations and focal hepatic lesions. 3. Quantification of the induced effects can be easily achieved by simple morphometric methods both for the nuclear enlargement and for the occurrence of focal hepatic lesions. 4. Proliferation-mediated effects on carcinogenesis are unlikely to affect the induction of foci in the IOCA. Similar to the partial hepatectomy in the Ito-model, the rapid growth of the embryonic liver provides such a high cell proliferation that a stimulating effect of the test substance is of little or no effect. Therefore, merely cytotoxic effects are less likely to mimic carcinogenicity. 5. The pronounced proliferation of the embryonic tissue also contributes to the high sensitivity of the assay. The induction of regenerative proliferation in potential target tissues frequently introduced in animal experiments (36, 39) is not necessary in ovo due to the high proliferation rate of the embryonic tissue. 6. An additional non-rodent species strengthens the extrapolation of animal studies to humans. 7. Finally, there is less potential of human exposure during the experiment: There is no excretion of the injected carcinogens from the eggs. The egg shell may be regarded as a barrier, at least, for the non-volatile chemicals. The amounts of the carcinogenic chemicals that are needed for the IOCA are relatively small as compared to animal experiments.

It may be possible to study carcinogenic effects of chemicals in tissues other than the liver by the IOCA. However, the liver has been the favorite target organ studied in chemically-induced carcinogenesis (17). As more experience with different chemicals and different target tissues is gained the IOCA may become an increasingly valuable tool both for toxicologic carcinogenicity testing and for research on the mechanisms of chemical carcinogenesis.