Mutagenicity of formaldehyde in Chinese hamster lung fibroblasts: synergy with ionizing radiation and N-nitroso-N-methylurea.
Cultured Chinese hamster V79 cells, a widely utilized model system in risk assessment of environmental agents, have been utilized to measure toxicity and mutagenicity of formaldehyde with or without previous exposure to either the alkylating agent N-nitroso-N-methylurea or to ionizing radiation. Each of these agents caused a dose-dependent decrease in colony forming efficiency and a parallel increase in 6-thioguanine resistant colonies. Significant mutant frequencies were induced by 0.3 up to 1 mM formaldehyde, 2 and 4 Gy of radiation and 0.2 and 0.5 mM N-nitroso-N-methylurea. Exposure of cells to ionizing radiation or N-nitroso-N-methylurea followed by submutagenic concentrations of formaldehyde potentiated both the cytotoxicity and the mutagenicity as compared with the corresponding separate effects caused by each of these agents. Taken together, these studies clearly demonstrate genotoxic effects in vitro of three recognized carcinogens, i.e. formaldehyde, N-nitroso-N-methylurea and ionizing radiation. Moreover, the synergies now demonstrated in regards to cytopathic consequences indicate interactive effects between formaldehyde and these agents, representing both a chemical and a physical carcinogen.
Grafström
R C
RC
Department of Toxicology, Karolinska Institute, Stockholm, Sweden.
Hsu
I C
IC
Harris
C C
CC
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects*; D005557:Formaldehyde / Q000494:pharmacology / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000528:radiation effects*; D008770:Methylnitrosourea / Q000494:pharmacology / Q000633:toxicity*; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology / Q000633:toxicity*
D009153:Mutagens; D005557:Formaldehyde; D008770:Methylnitrosourea