Mechanism of induction of human chorionic gonadotropin in lung tumor cells in culture. Increased levels of alpha-human chorionic gonadotropin-specific mRNA sequences and benzo(a)pyrene-induced hypomethylation.
Human lung cells (ChaGo) derived from a bronchogenic carcinoma produce human chorionic gonadotropin (hCG), predominantly the alpha subunit of the glycoprotein hormone, under culture conditions. Treatment of the cells with the polycyclic aromatic hydrocarbons, benzo(a)pyrene (BaP) or dimethylbenzanthracene, at concentrations which do not affect cell growth or macromolecular synthesis, stimulates the production of hCG in these cells. The levels of alpha hCG-specific mRNA (mRNA alpha hCG) sequences in total poly(A)+ RNA isolated from control and drug-treated ChaGo cells are determined by the dot hybridization technique using 32P-labeled, cloned cDNA alpha hCG probe. A concentration-dependent increase in the levels of mRNA alpha hCG sequences in BaP or dimethylbenzanthracene-treated ChaGo cells has been observed. The increase in the level of mRNA alpha hCG sequences can be detected after treatment of the cells with either of the drugs for 24 h, and this level attains its maximum within 48-72 h following drug treatment. A comparative study of the restriction endonuclease (MspI/HpaII) digestion patterns of the control and BaP-treated cell DNA suggests that the internal "C" residues of the -CCGG- sequences in the alpha hCG gene of untreated cells are highly methylated; whereas the internal C residues of the same MspI/HpaII recognition sequences in the alpha hCG gene are comparatively less methylated in BaP-treated cell DNA.
D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002283:Carcinoma, Bronchogenic / Q000378:metabolism*; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000096:biosynthesis* / Q000235:genetics; D005796:Genes / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D001580:Benzopyrenes; D002273:Carcinogens; D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D001564:Benzo(a)pyrene