DNA-protein crosslinks and p53 protein expression in relation to occupational exposure to formaldehyde.

BACKGROUND: Formaldehyde (FA) is classified as a probable human carcinogen. AIMS: To examine DNA protein crosslinks (DPC) and p53, which are generally known to be involved in carcinogenesis, in peripheral blood lymphocytes of workers exposed to FA. METHODS: DPC and p53 ("wild type" and mutant) were examined in peripheral blood lymphocytes of 186 workers exposed to FA (mean years of exposure = 16) and 213 unexposed workers. Every worker completed a questionnaire on demographic data, occupational and medical history, smoking, and hygiene. RESULTS: The adjusted mean level of DPC in the exposed and the unexposed workers differed significantly. Adjustment was made for age, sex, years of education, smoking, and origin. Exposure to FA increased the risk of having a higher level of pantropic p53 above 150 pg/ml (OR 1.6, 95% CI 0.8 to 3.1). A significant positive correlation was found between the increase of pantropic p53 protein and mutant p53 protein, as well as between pantropic p53 >150 pg/ml and mutant p53 protein. In the exposed group a significantly higher proportion of p53 >150 pg/ml was found among workers with DPC >0.187 (55.7%) (0.187 = median level of DPC) than among workers with DPC < or =0.187 (33.3%). The risk of having pantropic p53 protein >150 pg/ml was determined mainly by levels of DPC. Workers with DPC above the median level had a significantly higher risk of having pantropic p53 >150 pg/ml (adjusted OR 2.5, 95% CI 1.2 to 5.4). CONCLUSIONS: Results suggest that DPC and mutation in p53 may represent steps in FA carcinogenesis and a possible causal relation between DPC and mutation in p53. These biomarkers can be applied in the assessment of the development of cancer due to FA exposure.

Frequency of sister-chromatid exchange among greenhouse farmers exposed to pesticides.

Sister-chromatid exchange (SCE) was measured in peripheral lymphocytes of 104 greenhouse farmers exposed to pesticides and 44 unexposed workers. The results of SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and, (b) proportion of high frequency cells (cells with more than eight SCEs). A high correlation was found between these two variables. The adjusted means of both SCEs variables were significantly higher among the farmers compared with the unexposed group (P < 0.01). Adjustment was made for smoking, age, education, and origin. The adjusted means of both SCE variables, were significantly elevated (P < 0.05) among the farmers who prepared and applied more than 70% of the pesticides by themselves compared with those who prepared and applied less than 70% of the pesticides by themselves. Both SCEs variables were also significantly elevated (P < 0.05) among farmers who were involved in more than 7.4 sprays per year compared with those with 7.4 or less sprays per year (P < 0.05). We found a tendency towards elevation of the two variables of SCEs among those who did not use protective measures while preparing the pesticides. Evaluation of the influence of years of exposure on the frequency of SCEs showed that the two variables of SCEs were higher among those farmers who were exposed to pesticides for more than 21 years than among those with less than 21 years of exposure. The variables that had the most influence on the elevation of SCEs were self-preparation of the pesticide mixtures and the number of sprayings per year. Because the farmers used a mixture of almost 24 different chemical classes it was impossible to attribute exposure to a specific pesticide or group of pesticides to single farmers. Our finding of a significant increase of SCEs frequency in peripheral lymphocytes in greenhouse farmers indicates a potential cytogenetic hazard due to pesticides exposure.

Hematological changes in hospital workers due to chronic exposure to low levels of ethylene oxide.

We conducted a cross-sectional study to determine whether occupational exposure to low levels of ethylene oxide can cause hematological abnormalities. Blood samples were collected from a group of 47 hospital workers who were exposed to ethylene oxide during a mean period of 6.6 years (standard error, 1.1). Ethylene oxide range levels measured were < 0.01 to 0.06 ppm. The control group, individually matched by age, sex, and smoking habits, consisted of 88 workers from the administrative sector. We found significant differences between the exposed and the control group in the frequency of workers with white blood cells lower than the normal range. Although there was no significant difference in the absolute mean number of the total white blood cells, we found an elevation in the absolute mean number of monocytes and eosinophils (P < 0.01) and a decrease (P < 0.01) in the absolute mean number of lymphocytes in the exposed group compared with the control group. We also found an elevation (P < 0.01) in the percentage of hematocrit and the mean absolute number of the red blood cells, and a decrease (P < 0.01) in the mean absolute number of platelets, in the exposed group compared with the control group. The mean absolute number of eosinophils, red blood cells, and percentage of hematocrit was significantly higher, and the mean absolute number of lymphocytes and platelets was significantly lower, in the subgroups with a higher cumulative dose of exposure. A positive dose-response was found between cumulative dose exposure and the absolute mean number of eosinophils. In view of our findings, we suggest that the use of complete blood cells with differential in routine medical surveillance and for early detection of hygiene problems should be reexamined with special attention to the eosinophils count.

Prevalence of melanocytic nevi and freckles in young Israeli males. Correlation with melanoma incidence in Jewish migrants: demographic and host factors.

The role of host and environmental factors in the pathogenesis of multiple melanocytic nevi, atypical nevi, and freckles was studied in 1989 in a random sample of 3,040 Israeli males aged 17 years. Multiple melanocytic nevi were significantly associated with family history of melanoma or multiple melanocytic nevi (odds ratio (OR) = 15.0), fair or lightly pigmented skin color (OR = 2.7 and 2.3, respectively), and affiliation to the high or heterogenous melanoma risk group, determined by the incidence rates of melanoma in Jewish migrants from corresponding origin (OR = 3.1 and 2.1, respectively). An environment-related effect may account for the increased multiple melanocytic nevi risk among second- (OR = 8.2) compared with first-generation, native-born recruits (OR = 3.0) from the high melanoma risk group whose families had been living in Israel the longest. Atypical nevi were associated with fair (OR = 6.1) and lightly pigmented (OR = 3.5) skin color, high and moderate sunburn susceptibility (OR = 4.7 and 2.5, respectively), and family history of melanoma or multiple melanocytic nevi (OR = 4.7). Freckles were significantly associated with sun-sensitive phenotype, family history of melanoma or multiple melanocytic nevi (OR = 1.5). Conservative (OR = 1.9) or nonreligious status (OR = 1.9), and high (OR = 2.4) or heterogenous melanoma risk groups (OR = 1.8). These findings indicate that environmental factors may modify the occurrence of multiple melanocytic nevi and freckles in genetically susceptible ethnic groups.

Cause-specific mortality among Israeli adolescents in the 1980s.

PURPOSE: Considerable mortality occurs during adolescence despite it being a relatively healthy period of life. Nationwide analysis of adolescent mortality data helps identify those sub-groups with higher-than-expected death rates, that may be amenable to preventive intervention programs. METHODS: Adolescent mortality in Israel during 1981-1986 is examined by age (10-14, 15-19 years), sex, population group (Jews, non-Jews), and cause of death. Data were abstracted primarily from special publications for 1981-1986. Recently available mortality updates for 1987-1989 were inspected and significant changes in mortality during the latter period have been included. RESULTS: Among an average of approximately 800,000 adolescents aged 10-19 years living in Israel during 1981-1986, the majority (77%) were Jews. Overall mortality was 36.7 per 100,000. Death rates were almost twice as high for males as for females, increased with age for all population subgroups, and were 63% higher for non-Jews compared with Jews. Accidents were the major cause of death among Israeli adolescents (37.7% of total mortality), with male-to-female rate ratio of 3.4. Mortality from all external causes, including accidents, suicide, homicide, and other external causes accounted for 50.6% of all deaths. Neoplasms were the next major cause of death. Israel and U.S. adolescent mortality rates were compared and showed similar trends. CONCLUSIONS: The non-Jewish minority adolescents, and most particularly the males, are at the highest risk of death. Preventive intervention programs should be targeted to the high-risk populations described.