IMMUNOCYTOCHEMICAL IDENTIFICATION OF DNA-ADDUCTS, O-6-METHYLGUANINE AND 7-METHYLGUANINE, IN RESPIRATORY AND OTHER TISSUES OF RAT, MOUSE ANDSYRIAN-HAMSTER EXPOSED TO 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE

Citation
J. Vanbenthem et al., IMMUNOCYTOCHEMICAL IDENTIFICATION OF DNA-ADDUCTS, O-6-METHYLGUANINE AND 7-METHYLGUANINE, IN RESPIRATORY AND OTHER TISSUES OF RAT, MOUSE ANDSYRIAN-HAMSTER EXPOSED TO 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE, Carcinogenesis, 15(9), 1994, pp. 2023-2029
Citations number
47
Categorie Soggetti
Oncology
Journal title
ISSN journal
01433334
Volume
15
Issue
9
Year of publication
1994
Pages
2023 - 2029
Database
ISI
SICI code
0143-3334(1994)15:9<2023:IIODOA>2.0.ZU;2-Q
Abstract
The present paper reports about an immunocytochemical inventory of the cell types involved in the metabolic activation of the tobacco-specif ic nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to a DNA methylating metabolite. The formation and distribution of the m ethylated DNA bases O-6-methylguanine (O-6-meGua) and 7-methylguanine (7-MeGua) were studied in respiratory tissues, oesophagus, liver, kidn eys, pancreas, small intestine, colon and prostate of rat, mouse and h amster 6 h after treatment with a single dose of 30 mg NNK/kg. The tis sue- and cell-specific distribution of O-6-meGua- and 7-meGua-specific nuclear staining showed the same patterns and were remarkably similar in rat, mouse and hamster in spite of the diverging spectra of MVK-in duced tumours in these species. In nasal tissue, a target for NNK-indu ced tumourigenesis in rat and hamster, but not in mouse, adduct-specif ic nuclear staining was observed in ah three species in sustentacular cells, Bowman glands, respiratory epithelial cells and serous glands. Both methylated DNA bases were also observed in basal cells of the olf actory epithelium of rat and (occasionally) hamster, but not in those of the mouse. In the trachea, a target for NNK-induced tumourigenesis in hamster only, substantial adduct-specific nuclear staining was foun d in basal epithelial and glandular cells of the hamster; in the same cells of rat and mouse only a weak nuclear staining was found. In the lung, a common target for NNK-induced tumourigenesis, the formation of O-6-meGua and 7-meGua was restricted predominantly to bronchial and p roximal bronchiolar epithelium. Nuclear staining in the rat was occasi onally found in alveolar cells and was also observed in hepatocytes. I n the three species investigated, O-6-meGua- and 7-MeGua-specific nucl ear staining was found in target and non-target tissues. Apparently, a nd in analogy with results obtained in other studies, the species-spec ific organotropy for tumour formation of M?TK is not exclusively deter mined by DNA methylation. Expanding methylation data with literature d ata on factors considered to be involved in tumour formation, namely p roliferation, toxicity and DNA repair among others, still did not lead to a satisfactory explanation for the species-specific organotropy ob served. Additional factors (yet to be identified), need to be taken in to account in order to explain (and predict) tumourigenic effects indu ced by monofunctional methylating agents.