Advances in cancer biomarkers as applied to chemical exposures: the ras oncogene and p21 protein and pulmonary carcinogenesis.
J Occup Med 1991 Sep; 33(9):951-955
A discussion was presented of the potential application of the ras oncogene and its protein product, p21, as markers for pulmonary carcinogenesis, particularly with respect to respiratory carcinogenic agents such as polycyclic aromatic hydrocarbons (PAHs). Three ras genes were isolated and revealed to have normal homologues on human chromosomes. Cultured cells could be transformed by activation of ras oncogenes through point mutations or over expression of normal protooncogenes. In-vitro and in-vivo animal studies demonstrated point mutational activation of ras genes by selected PAHs. These chemicals could also alter noncoding gene sequences, resulting in over expression. The protein product p21 was a constituent of the eukaryotic plasma membrane inner surface and was known to bind guanosine-triphosphate, to have guanosine- triphosphatase activity and to act as a G-protein in an unidentified pathway for signal transduction. Over expression of a mutant p21 resulted in cell transformation. Human and animal lung cancer tissues and cells revealed mutation, amplification and activation of ras oncogenes. Enhanced ras messenger-RNA production and p21 over expression were noted in some human lung cancers. Serum of animals and serum and urine of human cancer patients contained immunologically identifiable p21. Altered expression of p21 was noted in lung cancer patients exposed to PAHs through cigarette smoking. In workers with high PAH exposure, PAH DNA adducts in blood lymphocytes correlated with ambient exposures. One worker had elevated serum p21. Three of 16 other workers exposed to hazardous waste had abnormal serum p21 levels. One of these developed a premalignant colon lesion, and its removal resulted in normalization of serum p21. Elevated p21 preceded development of lung cancer in seven of 46 workers with respiratory carcinogen exposure. The authors conclude that p21 may be useful as an early marker for preclinical carcinogenesis in persons with respiratory carcinogen exposure.
JOCMA7; NIOSH-Publication; NIOSH-Grant; Cancer; Carcinogens; Occupational-exposure; Biological-monitoring; Lung-cancer; Polycyclic-aromatic-hydrocarbons; Oncogenesis; Nucleic-acid-replication; Protein-synthesis; Laboratory-animals
Environmental Sciences Columbia University Sch of PH 60 Haven Avenue/b-1 Level New York, NY 10032
Journal of Occupational Medicine
Columbia University New York, New York, New York