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© 1991 Oxford University Press

research-article

Detection of acrolein and crotonaldehyde DNA adducts in cultured human cells and canine peripheral blood lymphocytes by 32P-postlabeling and nucleotide chromatography

Vincent L. Wilson 1 2, Peter G. Foiles 3, Fung-Lung Chung 3, Andrew C. Povey 4, Anthony A. Frank 5 and Curtis C. Harris 6

1Molecular Genetics/Oncology Laboratory, Department of Pathology and The Children's Hospital Kempe Research Center, The Children's Hospital and the Department of Pathology, University of Colorado Health Sciences Center Denver, CO 80218
3Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation Valhalla, NY 10595, USA
4Carcinogenesis Department, Paterson Institute for Cancer Research Manchester M20 9BX, UK
5School of Veterinary Medicine, Oregon State University Corvallis, OR 97331
6Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute NIH, Bethesda, MD 20892, USA

2To whom correspondence should be addressed at: Molecular Genetics/Oncology Laboratory, B120, The Children's Hospital, 1056 E. 19th Ave., Denver, CO 80218-1088, USA

People are constantiy being exposed to toxic and carcinogenic aldehydes. However, little is actually known about the mechanisms underlying the toxic and carcinogenic effects of these aldehydes on human cells. The DNA alkylating activities of two of the more toxic and environmentally prominent {alpha},ß unsaturated aldehydes, acrolein and crotonaldehyde, have been studied utilizing 32P-postlabeling and nucleotide chromatographic techniques. Several putative adducts were observed in DNAs isolated from acrolein- and crotonaldthyde treated human fibroblasts. One of these acrolein-DNA adducts was tentatively identified as the cyclic 1,N2-hydroxypropanodeoxyguanosine product, 3-(2'-deoxyribosyl)- 5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10-one, by co-chromatography with a chemical standard. The 1,N2 hydroxypropanodeoxyguanosine along with other possible adducts, was also found in DNA isolated from peripheral blood lymphocytes obtained from a dog 1 h after receiving a therapeutic dose of 6.6 mg/kg of cyclophosphamide. These results not only demonstrate the presence of acrolein and crotonaldehyde DNA adducts in treated human cells, but also suggest that these sensitive techniques may be useful to the study of the importance of acrolein to both the carcinogenic and antineoplastic activities of cyclophosphamide and other oxazaphosphorine mustards.


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