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DNA adduct measurements, cell proliferation and tumor mutation induction in relation to tumor formation in B6C3F1 mice fed coal tar or benzo[a]pyrene.
- Source :
-
Carcinogenesis [Carcinogenesis] 2000 Jul; Vol. 21 (7), pp. 1433-40. - Publication Year :
- 2000
-
Abstract
- Coal tar is a complex mixture containing hundreds of compounds, at least 30 of which are polycyclic aromatic hydrocarbons, including the carcinogen benzo[a]pyrene (BaP). Although humans are exposed to complex mixtures on a daily basis, the synergistic or individual effects of components within a mixture on the carcinogenic process remain unclear. We have compared DNA adduct formation and cell proliferation in mice fed coal tar or BaP for 4 weeks with tumor formation in a 2 year chronic feeding study. Additionally, we have analyzed tumor DNA for mutations in the K-ras, H-ras and p53 genes. In the forestomach of mice fed either coal tar or BaP an adduct indicative of BaP was detected, with adduct levels increasing in a dose-responsive manner. K-ras mutations were detected in the forestomach tumors, with the incidence being similar in mice fed coal tar or BaP. These results suggest that the BaP within coal tar is associated with forestomach tumor induction in coal tar-fed mice. DNA adduct levels in the small intestine were not predictive of tumor incidence in this tissue; instead, the tumors appeared to result from compound-induced cell proliferation at high doses of coal tar. K-ras mutations were detected in lung tumors. Since lung tumors were not increased by BaP, coal tar components other than BaP appear to be responsible for the tumors induced in this tissue. H-ras mutations, primarily occurring at codon 61, were the most common mutation observed in liver tumors induced by coal tar. Since this mutation profile is observed in spontaneous hepatic tumors, components in the coal tar may be promoting the expansion of pre-existing lesions.
- Subjects :
- Animals
Benzo(a)pyrene metabolism
Carcinogens metabolism
Cell Division drug effects
Coal Tar metabolism
DNA Mutational Analysis
DNA, Neoplasm drug effects
DNA, Neoplasm genetics
DNA, Neoplasm metabolism
Female
Gastric Mucosa metabolism
Genes, p53 drug effects
Genes, p53 genetics
Genes, ras drug effects
Genes, ras genetics
Intestine, Small cytology
Intestine, Small drug effects
Intestine, Small metabolism
Liver drug effects
Liver metabolism
Lung drug effects
Lung metabolism
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Neoplasms, Experimental metabolism
Neoplasms, Experimental pathology
Stomach cytology
Stomach drug effects
Benzo(a)pyrene toxicity
Carcinogens toxicity
Coal Tar toxicity
DNA Adducts biosynthesis
Mutation
Neoplasms, Experimental chemically induced
Neoplasms, Experimental genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0143-3334
- Volume :
- 21
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 10874023