Dose-response relationships of the tumorigenicity of cyclopenta[cd]pyrene, benzo[a]pyrene and 6-nitrochrysene in a newborn mouse lung adenoma bioassay.

Abstract

Cyclopenta[cd]pyrene (CPP) was a potent tumorigen when tested over a 5-fold dose range in the newborn mouse assay. A 20-fold increase in lung tumor multiplicity and a nearly 8-fold increase in tumor incidence was observed at the lowest total dose tested (1.55 mumol) with the dose-response relationship indicating a saturation of tumor multiplicity at approximately 7 tumors/animal. No liver nodules or lymphatic system tumors were noted. Analysis of dose-response data for benzo[a]-pyrene (BaP) and 6-nitrochrysene (6-NC) showed that tumor multiplicity for BaP also saturated at approximately 7 tumors/animal, whereas no similar saturation was found for 6-NC at up to 40 tumors/animal. Progression of lung adenomas to adenocarcinomas, as measured by the incidence of mice bearing malignant tumors, was essentially a linear function of dose. To facilitate comparison and maximize quantitative data obtainable from the newborn mouse assay-parameters were defined for tumor incidence (ED50), tumor multiplicity (TM1.0) and tumor malignancy (malignancy index). Values for the ED50 and TM1.0 were similar for the same compound and a tumorigenic potency series of 6-NC greater than BaP greater than CPP was obtained corresponding to a ratio of approximately 1:10-25:76.5-135, respectively. The malignancy index, however, indicated increased adenocarcinoma induction in the order CPP greater than 6-NC greater than BaP as expressed by the ratio 1:1.4:8.3, respectively.

• Authors: W F Busby Jr, E K Stevens, E R Kellenbach, J Cornelisse, J Lugtenburg
• Journal: Carcinogenesis (Carcinogenesis) Vol. 9 Issue 5 Pg. 741-6 (May 1988) ISSN: 0143-3334 [Print] England
• PMID: 3365834 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carcinogens
• Chrysenes
• Phenanthrenes
• Pyrenes
• cyclopenta(c,d)pyrene
• Benzo(a)pyrene
• 6-nitrochrysene

Topics

• Adenoma (chemically induced)
• Animals
• Animals, Newborn
• Benzo(a)pyrene
• Biological Assay (methods)
• Carcinogens
• Chrysenes (toxicity)
• Dose-Response Relationship, Drug
• Female
• Lung Neoplasms (chemically induced)
• Male
• Mice
• Mice, Inbred ICR
• Phenanthrenes (toxicity)
• Pyrenes (toxicity)
• Skin Neoplasms (chemically induced)