Carcinogenicity of benzo[a]pyrene and manufactured gas plant residues in infant mice

Abstract

The present study determined tumorigenicity, tumor classification and DNA damage induced in infant mice by benzo[a]pyrene (B[a]P) or Manufactured Gas Plant (MGP) residues after a single exposure. Male and female B6C3F1 mice were exposed to B[a]P or MGP residue from a single environmental site (MGP-4) and males were also exposed to MGP residue composite from seven different sites (MGP-M7). At 26, 39 and 52 weeks after exposure tumorigenesis was assessed in lung, forestomach and liver. Formation and persistence of DNA adducts were quantified by 32P-postlabeling. Exposure of males to B[a]P induced liver tumors in a dose and time dependent manner. MGP induced more advanced tumors than B[a]P. Only a single liver tumor was found in MGP-4 treated females. No forestomach and few pulmonary adenomas were induced in males or females. MGP-4, MGP-M7 or B[a]P induced DNA adducts in males and females. Adducts in liver, lung and forestomach peaked on different days and decreased at different rates. At 24 h post-exposure, no significant differences in initial DNA adduct levels occurred in males and females exposed to MGP-4 or B[a]P. Lack of DNA damage (adducted DNA) did not account for non-responsiveness of lung and forestomach in B6C3F1 genders as well as in liver in females. MGP tumorigenicity could not be accounted for solely by B[a]P content nor did it reflect additivity of B[a]P and other carcinogenic polycyclic aromatic hydrocarbons (PAHs) in MGP. Synergy among MGP-PAHs, presence of unidentified carcinogens and/or promoters in MGP may account for MGP potency. The B6C3F1 infant male model is a convenient and rapid assay for assessing MGP liver tumorigenicity and potency.

Fetal MouseCyp1b1and Transplacental Carcinogenesis from Maternal Exposure to Dibenzo(a,l)pyrene

“…Many environmental chemicals for which there are significant human exposures are transplacental carcinogens in rodents, including the food mutagen 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (6), benzo(a)pyrene (34), and the tobacco-specific carcinogen 4-(methynitrosamino)-1-(3-pyridyl)-1-butanone (4). The infant mouse has also been used as a cancer model with enhanced sensitivity compared with the adult for a number of chemical carcinogens such as diethylnitrosamine, PAHs, and aflatoxin B 1 (35)(36)(37). The sensitivity of the infant mouse to chemical carcinogens is relevant for the present discussion as we administered a very lipophilic carcinogen during late pregnancy in our model.…”

Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons

“…This difference could be explained by the fact that we used genotoxic data from human cancer cells, low doses of PAHs (nanomolar range), a global genotoxic measure and a new modeling method. Underestimated TEF values could partly explain the disparity between theoretical and practical genotoxic data for mixtures of PAHs (Rodriguez et al, 1997;Baird et al, 2005) and could result in an underestimation of risk. Nonetheless, our GEF values are similar to other published TEFs (Durant et al, 1996;Louiz et al, 2008;US-EPA, 2010) (Table 3), in particular for highly genotoxic and carcinogenic compounds DBahA (Nisbet and LaGoy, 1992), DMBA (Collins et al, 1998), and DBalP (Wynder and Hoffmann, 1961).…”

Influence of fish smoking methods on polycyclic aromatic hydrocarbons content and possible risks to human health

“…It is known that in mammalian cells, PAHs undergo metabolic activation to diol, and epoxides that bind covalently to cellular macromolecules, including DNA, thereby causing errors in DNA replication and mutations that initiate the carcinogenic process (Rodriguez et al, 1997;Schoket, 1999;Lightfoot et al, 2000;Essumang et al, 2012Essumang et al, , 2013. Polymorphisms causing glutathione transferase deficiencies (GSTM1) may result in elevated breast cancer, lung cancer and other forms of human cancer risk from PAHs (IARC, 1999;Van der Hel et al, 2003).…”