Loss of heterozygosity analysis of mouse pulmonary adenomas induced by coal tar

Abstract

Manufactured gas plant (MGP) residues, commonly known as coal tars, were generated several decades ago as a byproduct of residential and industrial gas production from the distillation of coal. Previous short-term exposure studies have shown MGP residues to be tumorigenic in mouse liver and lung. In order to gain further insight into carcinogenesis by complex mixtures of environmental chemicals containing known carcinogenic polycyclic aromatic hydrocarbons, we investigated mouse pulmonary tumors for loss of heterozygosity (LOH) as a result of multiple exposure to MGP residues. Twenty mouse lung adenomas produced in (C57BL/6 x C3H)F1 hybrid mice and manually microdissected were selected to examine genome-wide allelic losses at 58 microsatellite loci. Regions of chromosomes 1, 4, 5, 8, and 11 were affected in 30-40% of tumors. The elevated rates of allelic imbalance in these chromosomes may indicate the location of unknown tumor suppressor genes significant to neoplastic transformation in mouse lung tissues. Laser capture microdissection-based LOH analysis of pulmonary adenomas showed that contamination of nonneoplastic tissues was not masking the allelic losses in the manually microdissected tumor analysis. The low frequency of chromosome instability in these tumors, measured by means of inter-simple sequence repeat PCR, suggests the presence of discrete regions of LOH instead of extensive structural rearrangements.

Carcinogenic Effects of MGP-7 and B[a]P on the Hamster Cheek Pouch

“…Since MGP residues are widely spread throughout nature, and the oral cavity is one of the first points of contact, we have considered it important to determine the carcinogenic effects of multiple doses of MGP on the HCP. We used here a well-characterized MGP mixture produced by mixing the residues of seven different sites (Goldstein et al 1998) and that has been used in other carcinogenic models (Benavides et al 2003; Culp et al 1998; Goldstein et al 1998; Rodriguez et al 1997; Weyand et al 1995). Based on the previous data of our collaborators, we expected MGP-7 to be carcinogenic in the HCP.…”