Oncogene and suppressor gene expression as a biomarker for ethylene oxide exposure

Ethylene oxide is a proven genotoxic chemical, and there is lots of evidence suggesting its carcinogenic effects in humans. The unexpected massive appearance of a certain tumorous cluster in personnel exposed to ethylene oxide in a Hungarian county hospital focused attention on the effects of this toxic gas. Since we had developed an animal model for the investigation of alterations in onco/suppressor gene expression due to external carcinogenic agents, and this model had already been used to evaluate the carcinogenic effects of cytostatic drugs in humans, an analysis of the effects of ethylene oxide exposure seemed to offer further information on the usefulness of gene expression as a biomarker. The main purpose of our study was to determine whether or not ethylene oxide exposure causes an elevated expression of onco/suppressor genes in the white blood cells of exposed people. Two different exposed groups and one control group were included in the study. The N-ras and p53 genes were chosen for the investigations of gene expression. N-ras is known to be activated in several tumor types, and p53 is also involved in carcinogenesis and plays an important role in the cellular answer mechanism to exogenous toxic effects. RNA was isolated from the white blood cells, slot blotted onto nitrocellulose membranes, and hybridized with chemoluminescently labeled gene probes. The results were detected on X-ray films and scanned into a computer, and relative risk for elevated gene expression was calculated in each group. Elevated N-ras and detectable p53 expressions were observed more frequently in both exposed groups compared with the control group (relative risks--N-ras: 1.57 [0.77-3.22] and 2.34 [1.21-4.52]; p53: 6.67 [2.35-18.92] and 6.06 [2.10-17.49]).