Evaluation of the newborn mouse model for chemical tumorigenesis

Abstract

A total of 45 chemicals, including two aromatic hydrocarbons, five aromatic amines, three azo dyes, ten nitroso compounds, three steroids, four tryptophan metabolites and their related compounds, four naturally occurring substances, four pyrolysates of amino acids and ten miscellaneous compounds, were tested for newborn mouse tumorigenesis assay (NMTA). The results of the NMTA were compared with data from 'Survey of Compounds Which Have Been Tested for Carcinogenic Activity', NIH, NCI, USA (SCWHBTCA), and also with data from the IARC Monographs (Vols 1-41), Lyon, France (IARC). Of the 45 chemicals tested by the NMTA, 28 chemicals showed positive results in the NMTA, and the remaining 17 chemicals were found to be negative for tumor development. The correlation of the results between the NMTA and the mouse and/or rat carcinogenesis test starting at young adult age reported in the SCWHBTCA and in the IARC were compared with 37 chemicals tested; the remaining eight chemicals were found only in our NMTA results. It can be concluded that 31 out of 37 chemicals (83.8%) tested by the NMTA showed similar carcinogenic or non-carcinogenic results obtained in either adult mouse and/or rat carcinogenesis tests. The remaining six chemicals showed contradictory results between the NMTA and either adult mouse and/or rat carcinogenesis tests. Those six chemicals were N-hydroxy-4-acetylaminobiphenyl, estradiol, 3-hydroxyanthranilic acid, 3-hydroxy-L-kynurenine, isonicotinic acid hydrazide and phenobarbital. Among the 37 chemicals, 34 were comparable with the results of the adult mouse carcinogenesis test and those of the NMTA. Twenty-nine out of 34 chemicals (85.3%) showed similar results to the adult mouse carcinogenesis test. Contradictory results were obtained with the following five chemicals: N-hydroxy-acetylaminobiphenyl, 3-hydroxy-anthranilic acid, 3-hydroxy-L-kynurenine, isonicotinic acid hydrazide and phenobarbital. There were 35 chemicals which were comparable with the results of the adult rat carcinogenesis test, and 32 chemicals showed the same results as the NMTA (91.4%). Dissimilar results were obtained with the following three chemicals: estradiol, 3-hydroxy-anthranilic acid and phenobarbital. Based on the results presented in this report, it is reasonable to conclude that the NMTA is one of the most useful and reliable methods for detecting tumorigenic or non-tumorigenic chemicals, when a small amount of chemical is available for rodent carcinogenesis test and the duration of the study is limited to 1 year.

Critical Windows of Exposure for Children's Health: Cancer in Human Epidemiological Studies and Neoplasms in Experimental Animal Models

“…These include urethane and ENU for causation of Harderian gland tumors in mice (Table 16); ENU and renal mesenchymal tumors in rats (Table 13); 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and lung and liver tumors in mice (Tables 9, 10, and 11); irradiation, urethane, and ENU and lymphoid tumors in mice (Table 11); radiation, ENU, benzidine, and safrole and liver tumors in mice (Table 17); 3'-azido-3'-deoxythymidine and mammary tumors in mice (Table 18); radiation and osteosarcoma in mice (Table 19), radiation and thyroid tumors in dogs (Table 20), and DES and uterine tumors in mice (Table 21). Certain types of tumors are more readily caused in adult than in neonatal animals (194), and certain chemicals are more effective in adult than in neonatal mice (195). Progressive acquisition of differentiated characteristics is among the several possible contributing factors, along with numbers of cells at risk and effective dose.…”

Metabolic Activation Capacity of Neonatal Mice in Relation to the Neonatal Mouse Tumorigenicity Bioassay

“…Various classes of genotoxic chemical carcinogens have been studied, including polycyclic aromatic hydrocarbons (PAHs) [9,10,[36][37][38], halogenated PAHs [33,39], nitrated PAHs [40][41][42], food pyrolysis products (heterocyclic amines) [30,31], complex environmental mixtures [43,44], nitrosamines [34], mycotoxins [34], vinyl compounds [34], azo dyes [34], aromatic amines [34], and allylarenes, including estragole and safroles [34].…”

“…For example, Fujii [38] reviewed the tumorigenicity results of 45 compounds tested using the ICR/Ha, ICR/Jcl (ICR), and CDF1 (BALB/c ϫ DBA/2) mouse strains. Of the 45 chemicals tested in both male and female mice, 28 chemicals were found to be tumorigenic and the other 17 chemicals were nontumorigenic.…”

4‐Aminobiphenyl induces liver DNA adducts in both neonatal and adult mice but induces liver mutations only in neonatal mice

“…Such a delay in chemical elimination may result in a greater chance of changing normal cells into mutant and ultimately tumor cells. 13 Young animals also have faster cell turnover rates, and the faster rates of cell replication may further increase the sensitivity of neonatal animals to carcinogens. The importance of cell proliferation at the time of carcinogen treatment was demonstrated previously.…”