Biomedical subjects

D C Christiani

Publications and source records attributed to D C Christiani.

At least 37 records · Page 2Linked to original sources

PubMed2001

p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer.

The p16(INK4a) protein inhibits cyclin-dependent kinase 4, a key regulator of progression through the G(1) phase of the cell cycle. Methylation of CpG islands in the promoter region is an important avenue for inactivation of p16. The mechanism of methylation of the p16 promoter region, however, has not been elucidated. Recent reports investigating p16 methylation in non-small cell lung cancer (NSCLC) suggest that carcinogens in tobacco smoke induce the DNA methylation process. We investigated the association between methylation of the p16 promoter region and exposure to tobacco smoke in 185 primary NSCLCS: We also studied the relationship of p16 methylation with mutation of the K-ras and p53 genes, as well as with methylation at the DAP-kinase and p14(ARF) loci. Finally, we evaluated the prognostic significance of p16 methylation in NSCLC. The prevalence of p16 methylation was greater in squamous cell carcinoma (41%) compared with adenocarcinoma (22%; P = 0.03; Fisher's exact test). Methylation of p16 was significantly associated with pack-years smoked (P = 0.007; Wilcoxon rank sum test), duration of smoking (P = 0.0009; Wilcoxon rank sum test), and negatively with the time since quitting smoking (P = 0.03; Wilcoxon rank sum test). No methylation of the nearby p14(ARF) locus was detected, and methylation of the DAP-kinase locus was not associated with either p16 methylation or with exposure to tobacco smoke. In patients with stage 1 adenocarcinoma, p16 methylation was an independent risk factor predicting significantly shorter postsurgery survival (P = 0.03), controlling for the significant effects of other factors, including K-ras mutation. These findings suggest that methylation of CpG islands in tobacco-associated cancers occurs in a gene- and tissue-specific manner and is induced directly or indirectly by exposure to tobacco smoke in NSCLC.

Aged↗

PubMed2001

Promoter methylation of DAP-kinase: association with advanced stage in non-small cell lung cancer.

Death associated protein (DAP)-kinase is a 16 kDa calmodulin-dependent serine/threonine kinase that carries a death domain at its C-terminus. DAP-kinase functions as a positive mediator of apoptosis that is induced by interferon-gamma. Recent studies suggest that DAP-kinase is involved in tumor metastasis and that it can be inactivated by methylation of CpG islands in the promoter region of the gene in some human tumors. However, little is known about the factors that are associated with the occurrence of DAP-kinase promoter methylation. We investigated both the possible associations of tobacco carcinogen and asbestos exposure with DAP-kinase promoter methylation, and the demographic and clinical factors associated with DAP-kinase promoter methylation in non-small cell lung cancer (NSCLC). One hundred and eighty-five patients diagnosed with NSCLC undergoing surgical resection from June, 1992 through December, 1996 at Massachusetts General Hospital participated in this study. Methylation-Specific PCR (MSP), performed using fresh-frozen tissue, was used to determine the methylation status of the promoter region of the DAP-kinase gene. Forty-seven (25%) of 185 tumors showed DAP-kinase promoter methylation. There was a significant association between methylation and an advanced pathologic stage (P=0.003, Fisher's exact test). Methylation of the DAP-kinase promoter was also associated with an increase in tumor size (P=0.009, Fisher's exact test) and lymph node involvement (P=0.04). No association was found between promoter methylation of DAP-kinase and k-ras or p53 mutation. In addition there was no association with a history of exposure to tobacco or asbestos. Controlling for age, sex, and histology, the odds ratios describing the association of DAP-kinase hypermethylation with stage were 2.70 (1.13--6.45), 3.11 (1.37--7.08) and 7.77 (1.21--50.03) in stages II, III and IV, respectively. Stage I cases with DAP-kinase promoter methylation had worse overall survival, but with the small sample size and limited follow-up this did not reach statistical significance. Our findings suggest that methylation of the promoter region of the DAP-kinase gene is not associated with exposure to tobacco or asbestos. However, they strongly suggest that DAP-kinase may be important in the progression of non-small cell lung cancer from early to late stage disease.

Adult↗

PubMed2001

Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer.

The short arm of chromosome 3 is thought to harbor a novel oncogenic locus that is important in the genesis of lung cancer. The region at 3p21 is believed to contain a distinct locus that is sensitive to loss from the action of tobacco smoke carcinogens and has been reported to be specifically targeted for deletion in lung cancer. To investigate whether 3p21 alteration in lung cancer is associated with carcinogen exposure, PCR-based analysis was performed to detect loss of heterozygosity (LOH) on chromosome 3 at 3p21 in non-small cell lung carcinoma (NSCLC). We also measured instability at the BAT-26 locus, because the mismatch DNA repair gene, hMLH1, is found at 3p21. LOH at 3p21 was analyzed for association with the clinical features of NSCLC, p53 mutation status, polynuclear aromatic hydrocarbon-DNA adduct levels (measured using 32P-postlabeling) and carcinogen exposure information including cigarette smoking and asbestos exposure. Of 219 lung cancers, 150 cases (68.5%) were informative at the D3S1478 locus, and 44.2% of squamous cell carcinoma cases and 30.2% of adenocarcinoma cases showed 3p21 LOH. None of the cancers showed BAT-26 instability. The prevalence of 3p21 LOH was higher in both current and former smokers compared with never smokers and was higher in p53 mutated cases. Among squamous cell carcinoma cases, there was a strong association of increased 3p21 LOH with increasing polynuclear aromatic hydrocarbon-DNA adducts levels (P = 0.03), as well as an increased prevalence LOH with earlier age of smoking initiation (P = 0.02). Our results confirm that 3p21 LOH is strongly associated with measures of biologically effective dose of exposure to tobacco carcinogens. Our results also suggest that alterations of hMLH1 are not related to any of the reported associations, because there was no evidence of microsatellite instability. Finally, LOH in 3p21 may be an early molecular event in NSCLC, because it is significantly associated with a tendency to start smoking at a young age.

Adenocarcinoma↗

PubMed2001

A prospective study of lung function among boilermaker construction workers exposed to combustion particulates.

BACKGROUND: Given the evidence of both acute cross-shift and short-term decrements in lung function in boilermaker construction workers following occupational exposure to combustion particulates, we sought to determine whether exposure is associated with an annual loss in lung function. METHODS: As part of an ongoing investigation, we conducted a 2-year longitudinal study of lung function among 118 boilermakers. Exposure was assessed with a work history questionnaire. Spirometry measurements were performed annually. RESULTS: We found an association between annual FEV(1) and hours worked at a gas-fired plant during the previous year, beta = - 9.8 mls/100 hours worked (95% CI: - 16.0, - 3.5) after adjustment for age, baseline FEV(1) and cigarette smoking status. The adjusted association between FEV(1) and "ever" worked at a gas-fired plant was - 99.7 mls (95% CI: - 154.8, - 44.5). There was also evidence of a negative association between FEV(1) and "ever" worked and hours worked at oil and coal-fired plants. CONCLUSIONS: These data suggest an association between annual lung function loss and working at gas, coal and oil-fired plants. Further follow-up of this cohort of boilermakers is in progress.

Adult↗

PubMed2001

Atopic asthma: differential activation phenotypes among memory T helper cells.

BACKGROUND: T cells have been implicated in the pathogenesis of atopic asthma. We have previously shown that memory T helper cells (CD4+CD45RO+) are preferentially activated relative to naïve T helper cells (CD4+CD45RA+) after bronchial allergen challenge. However, specific T helper subpopulations that are activated in atopy and/or asthma remain undefined. OBJECTIVE: To determine the T helper subpopulations and activation phenotypes relevant to acute and stable asthma that may be common with or distinct from atopy. METHODS: Two groups of atopic asthmatics (ten acute and nine stable asthmatics) and two non-asthmatic groups (14 non-asthmatic atopics and eight normal non-atopic controls) were analysed. Ten acute asthmatics were assessed in the emergency room during an acute episode (FEV1 43.6% +/- 18.4). Nine stable asthmatics were assessed during a symptom-free period (FEV1 85% +/- 6). Using multiple colour flow cytometry we analysed T cell subpopulations and the expression of IL-2-receptor (IL-2R) and MHC-class II antigens (MHC II) on naïve and memory T helper cells in the peripheral blood of asthmatic and non-asthmatic groups. RESULTS: Atopic asthmatics (acute and stable) had an increased percentage of memory T helper cells expressing IL-2R compared with normal non-atopics (mean SD 16.1 +/- 6%, 12.4 +/- 2% and 7.7 +/- 1.8%, P < 0.05) but not compared with non-asthmatic atopics (10 +/- 3.5%). Naïve T helper cells had low expression of IL-2R and MHC II in all four groups. MHC II antigen expression was increased in memory T helper cells of asthmatics (acute and stable) compared with normal non-atopics (13.9 +/- 7.5, 10.6 +/- 5 and 4.9 +/- 2.5, P < 0.05) but not compared with non-asthmatic atopics (7.92 4). A novel finding was that IL-2R and the MHC II molecules were mainly expressed in non-overlapping populations and coexpression was found predominantly on memory T helper cells. Asthmatics (acute and stable) had higher proportion of double positive memory T helper cells (IL-2R+MHC II+) compared with both non-asthmatic groups (P < 0.05). CONCLUSIONS: We demonstrate a differential expression of IL-2R+ and MCH II+ on CD45RO+ T helper cells that would suggest that there are three subsets of activated memory T helper cells in asthmatics. Two non-overlapping IL-2R+ or MHC II+ CD45RO+ T helper cells and a third subpopulation of activated cells that coexpress IL-2R and MHC II (double positives). This latter subpopulation is significantly higher in asthmatics (acute or stable) compared with both non-asthmatic groups, suggesting a specific T helper activation phenotype distinct to atopic asthmatics as compared with atopic non-asthmatics.

Acute Disease↗

PubMed2001

Body weight, alcohol consumption and liver enzyme activity--a 4-year follow-up study.

BACKGROUND: This prospective study was performed in order to investigate the effect of baseline body mass index (BMI), BMI changes, baseline alcohol consumption, and changes in alcohol consumption on liver enzyme activity. METHODS: This study population consisted of 6846 male workers in a steel manufacturing company who had undergone health examinations in 1994 and 1998. RESULTS: The risk for elevated both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values over the four years increased with the baseline BMI and BMI changes, but not with alcohol consumption. Compared with the subject BMI < 20, the adjusted odds ratios (OR) for those with baseline BMI 20-21.9, 22-24.9, 25- were 1.2, 1.6, 1.7 in AST and 1.4, 2.4, 2.8 in ALT, respectively. Compared with subjects who either lost or maintained their weight, the adjusted OR for men with slight, moderate, and heavy weight gain were 1.7, 2.6, 6.8 in AST and 2.4, 3.9, 11.3 in ALT, respectively. However gamma-glutamyl transferase (GGT) was associated with BMI changes and baseline alcohol consumption, not with baseline BMI and changes in alcohol consumption. Compared with subjects who lost or maintained weight, the adjusted OR for men with slight, moderate, and heavy weight gain were 2.4, 4.4 and 8.5, respectively. In comparison with non-drinkers, the adjusted OR for light, moderate and heavy drinkers were 1.8, 2.1 and 5.8, respectively. CONCLUSION: These data suggest that body weight, rather than alcohol consumption, may be the major factor in determining the serum level of liver enzymes. Even when body weight was not generally considered to be overweight, slight to moderate gains in weight were associated with increases in serum liver enzymes.

Adult↗

PubMed2001

Is air pollution a risk factor for low birth weight in Seoul?

Environmental factors contributing to reduced birth weight are of great concern because of the well-known relation of birth weight to infant mortality and adverse effects in later life. We examined the associations between air pollution exposures during pregnancy and low birth weight among all full-term births (gestational age 37-44 weeks) for a 2-year period (January 1996 through December 1997) in Seoul, South Korea. We evaluated these associations with a generalized additive logistic regression adjusting for gestational age, maternal age, parental educational level, parity, and infant sex. We used smoothing plots with generalized additive models to analyze the exposure-response relation for each air pollutant. The adjusted relative risk of low birth weight was 1.08 [95% confidence interval (CI) = 1.04-1.12] for each interquartile increase for carbon monoxide concentrations during the first trimester of pregnancy. The relative risks were 1.07 (95% CI = 1.03-1.11) for nitrogen dioxide, 1.06 (95% CI = 1.02-1.10) for sulfur dioxide, and 1.04 (95% CI = 1.00-1.08) for total suspended particles also for interquartile increase in exposure. Carbon monoxide, nitrogen dioxide, sulfur dioxide, and total suspended particle concentrations in the first trimester of pregnancy period are risk factors for low birth weight.

Adult↗

PubMed2001

The G to C polymorphism at -174 of the interleukin-6 gene is rare in a Southern Chinese population.

Interleukin-6 is thought to be involved in the pathogenesis of coal workers' pneumoconiosis. Recently, a functional G to C polymorphism at position -174 of the promoter of the IL-6 gene has been described. We examined the -174 polymorphisms in 259 retired Chinese men from Guangxi province (all retired coal miners). Only one GC heterozygous and no CC homozygous variants were found. Our results suggest that the frequency of the C allele in this Chinese population is lower than in Caucasian and east Indian populations.

5' Untranslated Regions↗

PubMed2001

Applying genomic technologies in environmental health research: challenges and opportunities.

Recent discoveries in molecular biology and genetics have made it possible for environmental health researchers to examine how genetic characteristics affect response to environmental exposures. Understanding such gene-environment interactions offers exciting possibilities for the prevention and control of environmentally induced diseases. Despite these potential benefits, the collection and analysis of genetic information in environmental health research presents many of the same ethical, legal, and social (ELSI) challenges found in other types of genetic research. In this article, we describe a number of ELSI challenges in environmental genomic research and the opportunities and responsibilities that accompany this research.

Environmental Health↗

PubMed2001

Effects of exposure to organic solvents on menstrual cycle length.

To investigate the association between organic solvent exposure and menstrual disturbance, we conducted a cross-sectional study among 1408 petrochemical workers in China. Based on an industrial hygiene evaluation, we classified the workshops according to the presence or absence of organic solvents (benzene, styrene, toluene, or xylene). We used logistic regression to estimate odds ratios and 95% confidence intervals for prolonged menstrual cycle length (oligomenorrhea: average cycle length > 35 days during the previous year) associated with the exposure. After adjustment for confounders, each additional year of work in an exposed workshop was associated with a 7% increase in oligomenorrhea (odds ratio, 1.07; 95% confidence interval, 1.00 to 1.14). Compared with no exposure, 3 or more years of exposure was associated with a 53% increase in oligomenorrhea (odds ratio, 1.53; 95% confidence interval, 1.00 to 2.34). We concluded that exposure to organic solvents is associated with a trend toward increased frequency of oligomenorrhea.

Adult↗

PubMed2001

Pulmonary function in long-term asbestos workers in China.

The relationship of pulmonary function to exposure to asbestos and radiographic abnormalities has been controversial, especially when smoking is present as a confounder. The aim of the study was to provide further understanding on the radiographic-physiologic associations in nonsmoking and smoking asbestos workers. Radiographic asbestosis, pleural lesion, and pulmonary function were studied in 269 Chinese asbestos workers, with average exposure years of 23 for male workers and 18 for female workers. Their functional data were compared with those of 274 controls without exposure to dust. Although most of the male workers were smokers, none of the female workers smoked. In comparison with controls, asbestos workers had significantly lower lung volume and diffusing capacity, irrespective of gender. Female workers and smoking male workers had lower measurements of forced expiratory volume in 1 second and instantaneous forced expiratory flow at 50% and 25% of forced vital capacity. After adjustment for relevant covariates, asbestos exposure, asbestosis, and pleural abnormalities were associated with decreased parameters of pulmonary function, including lung volume, diffusing capacity, and airway flow. These data indicate that asbestos-related functional defects manifested by lung restriction and mild airway obstruction correlate with exposure to asbestos and with parenchymal and pleural abnormalities, independent of smoking.

Adult↗

PubMed2001

Firefighters' hearing: a comparison with population databases from the International Standards Organization.

We investigated firefighters' hearing relative to general population data to adjust for age-expected hearing loss. For five groups of male firefighters with increasing mean ages, we compared their hearing thresholds at the 50th and 90th percentiles with normative and age- and sex-matched hearing data from the International Standards Organization (databases A and B). At the 50th percentile, from a mean age of 28 to a mean age of 53 years, relative to databases A and B, the firefighters lost an excess of 19 to 23 dB, 20 to 23 dB, and 16 to 19 dB at 3000, 4000, and 6000 Hz, respectively. At the 90th percentile, from a mean age of 28 to a mean age of 53 years, relative to databases A and B, the firefighters lost an excess of 12 to 20 dB, 38 to 44 dB, 41 to 45 dB, and 22 to 28 dB at 2000, 3000, 4000, and 6000 Hz, respectively. The results are consistent with accelerated hearing loss in excess of age-expected loss among the firefighters, especially at or above the 90th percentile.

Adult↗

PubMed2001

Spirometric surveillance in hazardous materials firefighters: does hazardous materials duty affect lung function?

We analyzed spirometry results for 351 male hazardous materials firefighters from 1996 to 1999 who underwent one or more annual medical surveillance/fitness for duty examinations: 276 (79%) technicians and 75 (21%) support members. Support members had a very limited potential for hazardous materials exposure and served as referents. In cross-sectional comparisons, the technicians' average forced vital capacity and forced expiratory volume in 1 second were either statistically better or not significantly different from that of the support members at all four examinations. Longitudinally, no statistically significant differences were seen for forced vital capacity. The mean percent of predicted forced expiratory volume in 1 second decreased by 3% for technicians (P = 0.029), support controls (P = 0.433), and the total cohort (P = 0.014). Although respiratory irritants are the most common type of exposure in hazardous materials releases, the results suggest that hazardous materials technicians do not lose pulmonary function at a more accelerated rate than support team firefighters.

Adult↗

PubMed2001

Prospective study of hepatic, renal, and haematological surveillance in hazardous materials firefighters.

OBJECTIVES: To evaluate possible health effects related to work with hazardous materials as measured by end organ effect markers in a large cohort over about 2 years, and in a subcohort over 5 years. METHODS: Hepatic, renal, and haematological variables were analysed from 1996-98 in hazardous materials firefighters including 288 hazardous materials technicians (81%) and 68 support workers (19%). The same end organ effect markers in a subcohort of the technicians were also analysed (n=35) from 1993-98. Support workers were considered as controls because they are also firefighters, but had a low potential exposure to hazardous materials. RESULTS: During the study period, no serious injuries or exposures were reported. For the end organ effect markers studied, no significant differences were found between technicians and support workers at either year 1 or year 3. After adjustment for a change in laboratory, no significant longitudinal changes were found within groups for any of the markers except for creatinine which decreased for both technicians (p<0.001) and controls (p<0.01). CONCLUSIONS: Health effects related to work are infrequent among hazardous materials technicians. Haematological, hepatic, and renal testing is not required on an annual basis and has limited use in detecting health effects in hazardous materials technicians.

Adult↗

PubMed2001

Longitudinal changes in pulmonary function and respiratory symptoms in cotton textile workers. A 15-yr follow-up study.

To evaluate the chronic effects of exposure to cotton dust, a 15-yr follow-up study in cotton textile workers was performed in Shanghai, China from 1981 to 1996. Testing occurred four times during the 15-yr period. The achieved follow-up rates were 76-88% of the original 447 cotton textile workers, and 70-85% of the original 472 silk textile workers (as a control group). Identical questionnaires, equipment, and methods were used throughout the study. The prevalence of byssinosis increased over time in cotton workers, with 15.3% at the last survey versus 7.6% at the baseline, whereas no byssinosis was found in silk workers. More workers in the cotton group consistently reported symptoms than in the silk group, although symptom reporting varied considerably from survey to survey. Cotton workers had small, but significantly greater, adjusted annual declines in FEV(1) and FVC than did the silk workers. Years worked in cotton mills, high level of exposure to endotoxin, and across-shift drops in FEV(1) were found to be significant determinants for longitudinal change in FEV(1), after controlling for appropriate confounders. Furthermore, there were statistically significant associations between excessive loss of FEV(1) and byssinosis, chest tightness at work, and chronic bronchitis in cotton workers. Workers who consistently (three or four of the surveys) reported byssinosis or chest tightness at work had a significantly greater 15-yr loss of FEV(1). We conclude that long-term exposure to cotton dust is associated with chronic or permanent obstructive impairments. Consistent reporting of respiratory symptoms, including byssinosis and chest tightness at work, is of value to predict the magnitude and severity of chronic impairments in textile workers.

Adult↗

PubMed2001

The NAD(P)H:quinone oxidoreductase 1 gene polymorphism and lung cancer: differential susceptibility based on smoking behavior.

We conducted a hospital-based case-control study of 814 lung cancer patients and 1123 controls to examine the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene polymorphism with lung cancer susceptibility. Using PCR-RFLP genotyping assay techniques, we analyzed DNA samples to detect the variant forms of the NQO1 gene in exon 6 on chromosome 16q. We examined the relationship between lung cancer odds and NQO1 genotypes after adjusting for age, gender, and smoking behavior using generalized additive modeling. We found no overall association between NQO1 genotypes and lung cancer susceptibility, regardless of age, gender, family history of cancer, or histological cell type. However, our data demonstrated that in both former and current smokers, there was an association between NQO1 genotypes and lung cancer susceptibility that was dependent upon cigarette smoking duration and smoking intensity. For both current and former smokers, smoking intensity was more important in predicting cancer risk than smoking duration for all of the genotypes. Among former smokers, individuals with the T/T genotype were predicted to have a greater cancer risk than those with the C/C genotype for smoking durations up to 37 years. The predicted cancer risk for former smokers with the C/T versus T/T genotype depended on both smoking intensity and smoking duration. Our results support the concept that differential susceptibility to lung cancer is a function of both an inheritable trait in NQO1 metabolism and individual smoking characteristics.

Adult↗

PubMed2001

The interaction between microsomal epoxide hydrolase polymorphisms and cumulative cigarette smoking in different histological subtypes of lung cancer.

Microsomal epoxide hydrolase (mEH) is involved in the metabolism of environmental and tobacco carcinogens. Smaller studies found inconsistent results in the relationship between mEH polymorphisms and lung cancer risk. We investigated the two polymorphisms of mEH in 974 Caucasian lung cancer patients and 1142 controls using PCR-RFLP techniques. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between mEH genotypes and lung cancer risk. The adjusted odds ratio (OR) of the very low activity genotype versus that of other genotypes combined was 1.00 [95% confidence interval (CI), 0.74-1.34]. However, gene-environment interaction analyses revealed that the ORs decreased as cumulative smoking (defined as square root of pack-years) increased. When pack-years = 0, the OR was 1.89 (95% CI, 1.08-3.28). When pack-years = 28.5, the OR was 1.00 (95% CI, 0.76-1.32), and when pack-years = 80, the OR decreased to 0.65 (95% CI, 0.42-1.00). When cases were stratified according to histological subtypes, the interaction between mEH genotype and cumulative smoking was statistically significant (P < 0.01) for the 222 squamous cell carcinoma cases, whereas it was not significant (P = 0.18) for the 432 adenocarcinoma cases. In conclusion, cumulative cigarette smoking plays a pivotal role in the association between mEH polymorphisms and lung cancer risk, altering the direction of risk (in the case of the very low activity genotype) from a risk factor in nonsmokers to a relatively protective factor in heavy smokers.

Adult↗

PubMed2000

Individual variability in the zinc inducibility of metallothionein-IIA mRNA in human lymphocytes.

The metallothionein-III gene (MT-IIA) is a major member of the human MT gene family. Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that bind and detoxify heavy metals. At least two different MT-IIA polymorphisms have been identified in humans, one or both of which may affect susceptibility to metal toxicity. The purpose of this study was to investigate whether these different genotypes affect the inducibility of MT-IIA mRNA in human lymphocytes treated with zinc (Zn), the major known inducer of MT-IIA in vitro. Fresh lymphocytes obtained from 16 healthy volunteers, aged 23-38 yr, were genotyped for the MT-IIA gene and tested for expression. A 43.5-bp HindIII-Taql fragment of the MT-IIA promoter was used to probe for the two known polymorphisms (a 7.8-kb vs. a 5.3-kb fragmnent, and a 1.7-kb vs. a 1.6-kb fragment). The allele frequencies of the 16 subjects were 14%, for 5.3-kb allele and 19% for 1.6-kb allele. In Northern blotting experiments, MT-II mRNA levels were induced over a wide range of Zn concentrations during 2-h exposures; specifcally, levels increased by 9- to 115-fold with exposure to 100 microM ZnCl, and by 16- to 311-fold with exposure to 200 microM ZnCl2. However, no significant differences in MT-IIA inducibility were found between the 7.8/5.3-kb allele pair (n = 4) and the 7.8/7.8-kb allele pair (n = 12) or between the 1.7/1.6-kb allele pair (n = 5) and the 1.7/1.7-kb allele pair (n = 11). Thus. MT-IIA is strongly inducible by Zn in human lymphocytes, but individual variations exceed those that can be attributed to the known promoter-region polymorphisms.

Adult↗