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Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20205
The effects of several aldehydes and peroxides on growth and differentiation of normal human bronchial epithelial cells were studied. Cells were exposed to formaldehyde, acetaldehyde, benzoyl peroxide (BPO), or hydrogen peroxide (HPO). The effect of each agent on the following parameters was measured: (a) clonal growth rate; (b) squamous differentiation; (c) DNA damage; (d) ornithine decarboxylase activity; (e) nucleic acid synthesis; (f) aryl hydrocarbon hydroxylase activity; and (g) arachidonic acid and choline release. None of the agents were mitogenic, and their effects were assessed at concentrations which reduced growth rate (population doublings per day) to 50% of control. The 50% of control concentrations for the 6-h exposure were found to be 0.065 mM BPO, 0.21 mM formaldehyde, 1.2 mM HPO, and 30 mM acetaldehyde. BPO-exposed cells were smaller than controls (median cell planar area, 620 sq µm versus 1150 sq µm), and acetaldehyde-exposed cells were larger than controls (median cell planar area, 3200 sq µm). All agents increased the formation of cross-linked envelopes and depressed RNA synthesis more than DNA synthesis. HPO caused DNA single-strand breaks, while formaldehyde and BPO caused detectable amounts of both single-strand breaks and DNA-protein cross-links. Other effects included increased arachidonic acid and choline release due to HPO. The similarities and differences of the effects of these aldehydes and peroxides to those caused by tumor promoters are discussed.
1 Present address: Baltimore Veterans Administration Medical Center, Baltimore, MD 21218.
2 Present address: Pulmonary Branch, Heart, Lung, and Blood Institute, Bethesda, MD 20205.
3 Present address: Culture Media Branch, Centers for Disease Control, Atlanta, GA 30333.
4 Present address: Department of Toxicology, Karolinska Institutet, S-104 01 Stockholm 60, Sweden.
5 To whom requests for reprints should be addressed, at Building 37, Room 2C05, National Cancer Institute, NIH, MD 20205.
Received 6/13/84. Revised 1/ 9/85. Accepted 1/31/85.
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