Environmentally prevalent polycyclic aromatic hydrocarbons can elicit co-carcinogenic properties in an in vitro murine lung epithelial cell model

Low molecular weight (LMW) polycyclic aromatic hydrocarbons (PAH) are the most abundant PAHs environmentally, occupationally, and are in cigarette smoke; however, little is known about their carcinogenic potential. We hypothesized that LMW PAHs act as co-carcinogens in the presence of a known carcinogen (benzo[a]pyrene (B[a]P)) in a mouse non-tumorigenic type II cell line (C10 cells). Gap junctions are commonly suppressed and inflammation induced during tumor promotion, while DNA-adduct formation is observed during the initiation stage of cancer. We used these endpoints together as markers of carcinogenicity in these lung adenocarcinoma progenitor cells. LMW PAHs (1-methylanthracene and fluoranthene, 1–10 µM total in a 1:1 ratio) were used based on previous studies as well as B[a]P (0–3 µM) as the classic carcinogen; non-cytotoxic doses were used. B[a]P-induced inhibition of gap junctional intercellular communication (GJIC) was observed at low doses and further reduced in the presence of the LMW PAH mixture (P < 0.05), supporting a role for GJIC suppression in cancer development. Benzo[a]pyrene diol-epoxide (BPDE)-DNA adduct levels were significantly induced in B[a]P-treated C10 cells and additionally increased with the LMW PAH mixture (P < 0.05). Significant increases in cyclooxygenase (Cox-2) were observed in response to the B[a]P/LMW PAH mixture combinations. DNA adduct formation coincided with the inhibition of GJIC and increase in Cox-2 mRNA expression. Significant cytochrome p4501b1 increases and connexin 43 decreases in gene expression were also observed. These studies suggest that LMW PAHs in combination with B[a]P can elicit increased carcinogenic potential. Future studies will further address the mechanisms of co-carcinogenesis driving these responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00204-017-2124-5) contains supplementary material, which is available to authorized users.