The difference between hypertension determined by self-report versus examination in the adult population of the USA: Continuous NHANES 1999-2016.

BACKGROUND: Studies have considered the validity of self-reported hypertension relative to hypertension detected by examination; no study has explored trends in the difference between these two measures. Our objective was to calculate these differences overtime within subpopulations of the USA. METHODS: We included non-Hispanic white, non-Hispanic black and Hispanic adults who participated in the National Health and Nutrition Examination Surveys from 1999 to 2016, in the analysis (N = 44 333). We subtracted self-reported hypertension from hypertension detected by examination to calculate blood pressure difference (BPD). We fit weighted linear regression models that included important covariates along with all combination of two- and three-way interactions to predict the BPD. We used the fitted lines of the models to depict the patterns of differences in the different subpopulations. RESULTS: Age ≥ 45 years, lack of annual clinical visit, body mass index (BMI) < 25 and time were important factors associated with increased BPD. CONCLUSIONS: People who are ≥ 45 years, have normal BMI, or do not have annual medical visits are more likely to have a bigger BPD. We can use the calculated BPD, to adjust estimates of the prevalence of self-reported hypertension.

The Relationship between Insulin Resistance and Spatial QRS-T Angle in American Adults.

BACKGROUND: Insulin resistance can impair the electrical conductivity of the heart. Spatial QRS-T axis reflects ventricular depolarization and repolarization. The relationship between insulin resistance and spatial QRS-T angle has not been examined in the general population. OBJECTIVE: We examined the relationship between insulin resistance and spatial QRS-T angle in an American population-based sample. METHODS: We used data collected from the National Health and Nutrition Examination Survey III (NHANES III), and a directed acyclic graph to select confounders. We fitted logistic regression models and adjusted for the effect of the confounders. We stratified all analyses by gender. RESULTS: The odds ratios (OR) of the abnormal QRS-T angle and their 95% confidence intervals (CI) for females and males were 1.08 (1.03-1.16) and 1.03 (0.96-1.11), respectively. A 5-unit increase in insulin resistance in females increased the odds of an abnormal QRS-T angle by 47% (OR = 1.47, 95% CI, 1.10-2.10); in males, a 5-unit increase in insulin resistance increased the OR by 17% (OR = 1.17, 95% CI, 0.82-1.70). CONCLUSIONS: Spatial QRS-T angle may be associated with insulin resistance, especially in women. The individuals with a higher insulin resistance value had higher odds for major adverse cardiovascular events. Nevertheless, the results of this study should be verified in prospective studies.

The association of metabolic syndrome and QRS|T angle in US adults (NHANES III).

BACKGROUND: Spatial QRS|T angle is a predictor of cardiovascular events. Those with metabolic syndrome have an increased risk of cardiovascular morbidity and mortality. This study investigated the association between metabolic syndrome and spatial QRS|T angle. METHODS: We obtained data from the National Health and Nutritional Examination Survey III on 6,249 adults. We calculated spatial QRS|T angle from the standard 12-lead electrocardiogram and classified it as abnormal, borderline, or normal. We identified metabolic syndrome if at least three of the following were present: abdominal obesity, elevated blood pressure, elevated triglycerides, decreased high-density lipoprotein (HDL), and impaired fasting glucose. We used weighted logistic regression to estimate the effect of metabolic syndrome and its components on QRS|T angle while stratifying by gender and adjusting for age, race, smoking status, heart rate, PR, QT, and QRS interval, and QRS amplitude. RESULTS: Among men and women, metabolic syndrome, the number of components present, elevated blood pressure, and impaired fasting glucose were positively associated with QRS|T angle. Among women, decreased HDL and abdominal obesity were also positively associated with QRS|T angle. CONCLUSIONS: This study suggests that persons with metabolic syndrome may be at increased risk for ventricular arrhythmias. The use of spatial QRS|T angle to assess this cardiovascular risk is warranted.

Excess lung cancer occurrence in poultry plants. Occupational risk factors: Findings for oncogenic viruses exposure and other occupational exposures.

Certain viruses naturally infect and cause cancer in chickens and turkeys. Humans are widely exposed. The viruses cause cancer in primates, and transform human cells in vitro, but it is not known if they cause cancer in humans, mainly because of the lack of epidemiologic evidence. We conducted cohort mortality studies of workers in poultry slaughtering/processing plants across the United States, because they have the highest human exposures. An excess of lung cancer and other deaths was recorded in the poultry workers. Here, we report on a case-cohort study of the lung cancer deaths nested within these cohorts, that was conducted to provide epidemiologic evidence linking these viruses with human cancer occurrence, while adjusting for possible confounders, including workplace chemical carcinogens. We obtained interviews for 339 lung cancer deaths and 457 controls, selected from our combined cohorts of 30,411 poultry plant workers and 16,405 non-poultry workers, belonging to United Food & Commercial Workers unions. Data was analyzed by both logistic regression and Cox regression, adjusting for smoking and other confounders. Lung cancer risk was independently associated with tasks or work areas indicative of exposure to both poultry oncogenic viruses and to workplace chemical carcinogens. The study provides an incremental piece of evidence (epidemiologic), indirectly linking the oncogenic viruses of poultry with the occurrence of cancer in humans, and thus may have public health implications, but the limitations highlighted must be considered. Confirmatory studies, particularly molecular studies providing definitive proof of poultry oncogenic retrovirus integration in human DNA are needed, before the findings observed in this study can be put into proper perspective.

High-normal blood pressure is associated with visit-to-visit blood pressure variability in the US adults.

OBJECTIVES: High-normal blood pressure and visit-to-visit blood pressure variability are common in clinical settings. They are associated with cardiovascular outcomes. No population based studies have assessed the association between these two phenomena. Our objective was to test the relationship of high-normal blood pressure with visit-to-visit blood pressure variability. DESIGN: A cross-sectional study. METHODS: We used data from the cross-sectional Third National Health and Nutrition Examination Survey to test the relationship between high-normal blood pressure and visit-to-visit blood pressure variability; we conducted multivariable regression analyses to evaluate the relationship between these two variables. RESULTS: The analysis included 6,071 participants. The participants' mean age was 37.16 years. The means of visit-to-visit systolic and diastolic blood pressure variability were 5.84 mmHg and 5.26 mmHg. High-normal blood pressure was significantly associated with systolic and diastolic blood pressure variability (p values <0.05). CONCLUSIONS: High-normal blood pressure is associated with visit-to-visit blood pressure variability. Additional research is required to replicate the reported results in prospective studies and evaluate approaches to reduce blood pressure variability observed in clinical settings among patients with high-normal blood pressure to reduce the subsequent complications of blood pressure variability.

Community Team-Based Care for Hypertension Management: A Public-Private Partnership in Rural Arkansas.

Hypertension is a major public health problem in Arkansas. Team-based care (TBC), delivered by health care professionals such as a nurse, dietician, social worker, or community health worker rather than a physician alone, has been shown to improve blood pressure control.

The Effect of Metformin Use on Left Ventricular Ejection Fraction and Mortality Post-Myocardial Infarction.

BACKGROUND: Animal studies showed that the use of metformin after myocardial infarction (MI) resulted in a protective effect on cardiac myocytes. In this study, we examined the effect of metformin in patients with diabetes mellitus (DM) on left ventricular ejection fraction (LVEF) and post-MI mortality. METHODS: We reviewed charts of patients with MI admitted to the UAMS medical center. Baseline characteristics and 12-month follow up data were collected. Patients were classified into three groups: Control group- no DM (n = 464), Metformin group- DM + MI (n = 88) and No-Metformin group- DM + MI (n = 168). First, we compared Metformin and No-Metformin groups to the Control group. Second, we performed propensity-score matching in patients with DM, and compared Metformin to No-Metformin groups. RESULTS: All-cause 30-day and 12-month mortality was significantly higher in the No-Metformin group compared to controls (13.5 vs 9.3% p = 0.03 at 30 days, 23.7 vs 15.9 % p = 0.03 at 12 months). However, all-cause 30-day and 12-month mortality were similar in the Controls and Metformin group (9.3 vs 6.8 % p = 0.93 at 30 days, 15.9 vs 11.4 % p = 0.97 at 12 months). Mean LVEF on presentation (45 % in the three groups) and at follow up (47.84, 46.38 and 43.62 % in Control, Metformin, and No-Metformin groups, respectively) were not statistically different. There were no significant differences in regard to re-hospitalization, re-intervention, new stroke, CHF development, new MI, or identifiable arrhythmias. Metformin was an independent predictor of lower 30-day and 12-month all-cause mortality in patients with DM (HR 0.25, p = 0.02 and HR 0.32, p = 0.01, respectively). In the matched analysis, 30-day all-cause mortality was significantly higher in the No-Metformin compared to the Metformin group (21.1 vs 8.8 %, p = 0.05). However the difference in 12-month all-cause mortality did not reach statistical significance (24.6 vs 15.8 %, p = 0.15). CONCLUSION: This proof-of-concept study shows that use of metformin in patients with DM is associated with lower 30-day all-cause mortality and tendency for a lower 12-month all-cause mortality following MI without discernible improvement in LVEF.

Obesity is associated with visit-to-visit systolic blood pressure variability in the US adults.

BACKGROUND: Evidence has accumulated showing that blood pressure variability is associated with cardiovascular disease. A substantial increase in the prevalence of obesity has been documented globally. Our objective was to examine the relation of total and central obesity on visit-to-visit blood pressure variability. METHODS: We used data collected from the cross-sectional Third National Health and Nutrition Examination Survey, to examine the association of visit-to-visit blood pressure variability with body mass index and waist circumference. RESULTS: The analysis included 14,988 participants. The participants' mean age was 43.45 years. Visit-to-visit systolic blood pressure variability was associated with a body mass index ≥30 and a large waist circumference (beta coefficients were 0.25 and 0.31, respectively, P-values < 0.01). Neither the bivariate nor the multivariable analyses showed significant relationships between the obesity indicators and diastolic blood pressure variability. CONCLUSIONS: Obesity is associated with visit-to-visit systolic blood pressure variability. Additional research is required to replicate the reported results in prospective studies and evaluate approaches to reduce blood pressure variability observed in clinical settings among obese persons to reduce its subsequent complications.

Environmental lead exposure is associated with visit-to-visit systolic blood pressure variability in the US adults.

PURPOSE: The association between environmental lead exposure and blood pressure variability, an important risk factor for cardiovascular disease, is unexplored and unknown. The objective of the study was to test the hypothesis that lead exposure is associated with blood pressure variability. METHODS: American participants 17 years of age or older from National Health and Nutrition Examination Survey III were included in the analysis. Participants' blood lead concentrations expressed as micrograms per deciliter were determined. The standard deviations of visit-to-visit systolic and diastolic blood pressure were calculated to determine blood pressure variability. Multivariable regression analyses adjusted for age, gender, race, smoking and socioeconomic status were employed. RESULTS: The participants' mean age and mean blood lead concentration were 42.72 years and 3.44 mcg/dl, respectively. Systolic blood pressure variability was significantly associated with environmental lead exposure after adjusting for the effect of the confounders. The unadjusted and adjusted means of visit-to-visit systolic blood pressure variability and the ß coefficient of lead exposure were 3.44, 3.33 mcg/dl, ß coefficient = 0.07, P < 0.01. CONCLUSIONS: This study documents a positive linear relationship between environmental lead exposure and systolic blood pressure variability. Screening adults with fluctuating blood pressure for lead exposure could be warranted.

ACB-PCR quantification of K-RAS codon 12 GAT and GTT mutant fraction in colon tumor and non-tumor tissue.

K-RAS mutation is being developed as a cancer biomarker and tumor K-RAS is being used to predict therapeutic response. Yet, levels of K-RAS mutation in normal and pathological tissue samples have not been determined rigorously, nor inter-individual variation in these levels characterized. Therefore, K-RAS codon 12 GAT and GTT mutant fractions were measured in colonic mucosa of individuals without colon cancer, tumor-distal mucosa, tumor-proximal mucosa, normal tumor-adjacent tissues, colonic adenomas, and carcinomas. The results indicate K-RAS codon 12 GAT mutation is present at measurable levels in normal appearing mucosa. All tumors carried K-RAS mutation, in most cases as a mutant subpopulation.

In vivo mutation analysis using the ΦX174 transgenic mouse and comparisons with other transgenes and endogenous genes.

The ΦX174 transgenic mouse was first developed as an in vivo Ames test, detecting base pair substitution (bps) at a single bp in a reversion assay. A forward mutational assay was also developed, which is a gain of function assay that also detects bps exclusively. Later work with both assays focused on establishing that a mutation was fixed in vivo using single-burst analysis: determining the number of mutant progeny virus from an electroporated cell by dividing the culture into aliquots before scoring mutants. We review results obtained from single-burst analysis, including testing the hypothesis that high mutant frequencies (MFs) of G:C to A:T mutation recovered by transgenic targets include significant numbers of unrepaired G:T mismatches. Comparison between the ΦX174 and lacI transgenes in mouse spleen indicates that the spontaneous bps mutation frequency per nucleotide (mf(n)) is not significantly lower for ΦX174 than for lacI; the response to ENU is also comparable. For the lacI transgene, the spontaneous bps mf(n) is highly age-dependent up to 12 weeks of age and the linear trend extrapolates at conception to a frequency close to the human bps mf(n) per generation of 1.7 × 10(-8). Unexpectedly, we found that the lacI somatic (spleen) bps mf(n) per cell division at early ages was estimated to be the same as for the human germ-line. The bps mf(n) in bone marrow for the gpt transgene is comparable to spleen for the lacI and ΦX174 transgenes. We conclude that the G:C to A:T transition is characteristic of spontaneous in vivo mutation and that the MFs measured in these transgenes at early ages reflect the expected accumulation of in vivo mutation typical of endogenous mammalian mutation rates. However, spontaneous and induced mf(n)s per nucleotide for the cII gene in spleen are 5-10 times higher than for these other transgenes.

Metabolic syndrome and P-wave duration in the American population.

PURPOSE: Metabolic syndrome has a high prevalence in the United States. P-wave duration is a valuable indicator for atrial electrical conduction. Abnormalities in atrial electrical conduction can predispose to atrial fibrillation. Our objective was to estimate the effect of metabolic syndrome on P-wave duration in a nationally representative sample. METHODS: We included 6499 adults who participated in the National Health and Nutrition Examination Survey III (1988-1994). We estimated the effect of metabolic syndrome and its components on P-wave duration after adjusting for confounders such as demographic and lifestyle variables. We stratified the analyses by gender. RESULTS: Irrespective of gender, participants with metabolic syndrome had a longer P-wave duration than that of those without it. In addition, we observed a positive linear dose-response relation between metabolic syndrome components and P-wave duration. CONCLUSIONS: Patients with metabolic syndrome had a longer P-wave duration. They might have been at a higher risk for atrial fibrillation and mortality; they need to be periodically checked by their health care providers. However, the results of this study should be confirmed in prospective studies.

The mRNA expression and histological integrity in rat forebrain motor and sensory regions are minimally affected by acrylamide exposure through drinking water.

A study was undertaken to determine whether alterations in the gene expression or overt histological signs of neurotoxicity in selected regions of the forebrain might occur from acrylamide exposure via drinking water. Gene expression at the mRNA level was evaluated by cDNA array and/or RT-PCR analysis in the striatum, substantia nigra and parietal cortex of rat after a 2-week acrylamide exposure. The highest dose tested (maximally tolerated) of approximately 44 mg/kg/day resulted in a significant decreased body weight, sluggishness, and locomotor activity reduction. These physiological effects were not accompanied by prominent changes in gene expression in the forebrain. All the expression changes seen in the 1200 genes that were evaluated in the three brain regions were < or =1.5-fold, and most not significant. Very few, if any, statistically significant changes were seen in mRNA levels of the more than 50 genes directly related to the cholinergic, noradrenergic, GABAergic or glutamatergic neurotransmitter systems in the striatum, substantia nigra or parietal cortex. All the expression changes observed in genes related to dopaminergic function were less than 1.5-fold and not statistically significant and the 5HT1b receptor was the only serotonin-related gene affected. Therefore, gene expression changes were few and modest in basal ganglia and sensory cortex at a time when the behavioral manifestations of acrylamide toxicity had become prominent. No histological evidence of axonal, dendritic or neuronal cell body damage was found in the forebrain due to the acrylamide exposure. As well, microglial activation was not present. These findings are consistent with the absence of expression changes in genes related to changes in neuroinflammation or neurotoxicity. Over all, these data suggest that oral ingestion of acrylamide in drinking water or food, even at maximally tolerable levels, induced neither marked changes in gene expression nor neurotoxicity in the motor and somatosensory areas of the central nervous system.

Using Machine Learning to Predict Progression in the Gastric Precancerous Process in a Population from a Developing Country Who Underwent a Gastroscopy for Dyspeptic Symptoms.

BACKGROUND: Gastric cancer is the fourth most common cancer and the third most common cause of cancer deaths worldwide. Morbidity and mortality from gastric cancer may be decreased by identification of those that are at high risk for progression in the gastric precancerous process so that they can be monitored over time for early detection and implementation of preventive strategies. METHOD: Using machine learning, we developed prediction models for gastric precancerous progression in a population from a developing country with a high rate of gastric cancer who underwent gastroscopies for dyspeptic symptoms. In the data imputed for completeness, we divided the data into a training and a validation test set. Using the training set, we used the random forest method to rank potential predictors based on their predictive importance. Using predictors identified by the random forest method, we conducted best subset linear regressions with the leave-one-out cross-validation approach to select predictors for overall progression and progression to dysplasia or cancer. We validated the models in the test set using leave-one-out cross-validation. RESULTS: We observed for all models that complete intestinal metaplasia and incomplete intestinal metaplasia were the strongest predictors for further progression in the precancerous process. We also observed that a diagnosis of no gastritis, superficial gastritis, or antral diffuse gastritis at baseline was a predictor of no progression in the gastric precancerous process. The sensitivities and specificities were 86% and 79% for the general model and 100% and 82% for the location-specific model, respectively. CONCLUSION: We developed prediction models to identify gastroscopy patients that are more likely to progress in the gastric precancerous process, among whom routine follow-up gastroscopies can be targeted to prevent gastric cancer. Future external validation is needed.

Association between Dietary Salt Intake and Progression in the Gastric Precancerous Process.

Gastric cancer is the third leading cause of cancer mortality worldwide. Studies investigating the effect of salt on gastric cancer have mainly used self-reported measures, which are not as accurate as sodium/creatinine ratios because individuals may not know the amount of salt in their food. Using data from a prospective cohort study, we investigated the effect of salt intake on progression to gastric precancerous lesions. Salt intake was estimated by urinary sodium/creatinine ratios, self-reported frequencies of adding salt to food, and total added table salt. We repeated the analyses among groups with and without Helicobacter pylori infection. We did not observe a positive association between salt intake, measured by urinary sodium/creatinine ratio, and overall progression in the gastric precancerous process (adjusted risk ratio (RR): 0.94; 95% confidence interval (CI) 0.76-1.15). We did observe an association between salt intake and increased risk for progression to dysplasia or gastric cancer overall (adjusted risk ratio (RR): 1.32; 95% confidence interval (CI): 0.96-1.81), especially among those who continued to have H. pylori infection at the five-month follow-up (adjusted RR: 1.53; 95% CI: 1.12-2.09), and among those who had persistent H. pylori infection over 12 years (adjusted RR: 1.49; 95% CI: 1.09-2.05). Salt intake may increase the risk of gastric dysplasia or gastric cancer in individuals with H. pylori infection.

The Association between Salt and Potential Mediators of the Gastric Precancerous Process.

BACKGROUND: The process by which salt affects the gastric precancerous process has not been adequately studied in humans. METHODS: We investigated the effects of salt on gastric inflammation, epithelial damage, the density of Helicobacter pylori infection, and gastric epithelial cell proliferation, all of which may be mediators between salt and gastric precancerous/cancerous lesions. These potential mediators were measured using gastric biopsies as: (a) the density of polymorphonuclear and mononuclear cells (gastric inflammation), (b) mucus depletion (gastric epithelial damage), and (c) the severity of H. pylori infection. Salt intake was measured with spot urine samples (using urinary sodium/creatinine ratios), self-reported frequency of adding salt to food, and as total added salt. RESULTS: The average sodium/creatinine ratio (at baseline and post-treatment at five months) was associated with increased epithelial damage over the 12-year follow-up period among those with a greater severity of chronic inflammation and among those with continued H. pylori infection after treatment at five months. This association was stronger when both severe gastric inflammation and H. pylori infection were present at five months (ß: 1.112, 95% CI: 0.377, 1.848). CONCLUSION: In humans, salt was associated with an increase in epithelial damage in stomachs with more severe previous H. pylori-induced chronic inflammation.

The relation of blood lead and QRS-T angle in American adults.

The QRS-T angle is a key ECG predictor for ventricular arrhythmia. Lead has a strong relation with cardiovascular diseases; however, no study has been conducted to investigate the association between lead exposure and QRS-T angle. Thus, we explored this association in a population-based representative sample: NHANES III. We used the standard 12-lead ECGs to calculate Spatial QRS-T angles. Blood lead concentration was measured using graphite furnace atomic absorption spectrophotometry method. We conducted multivariate weighted logistic regression to adjust for impaired fasting glucose, hypertension, poverty index, age, race, and smoking status. We found that when the log of blood lead increased by one unit, the odds of an abnormal QRS-T angle increased by 34% among men and 4% among women. We suggest the use of QRS-T angle deviation among those who are exposed to lead to detect individuals at risk for adverse cardiovascular outcomes such as arrhythmias.

Use of Electronic Nicotine Delivery Systems (ENDS) by pregnant women I: Risk of small-for-gestational-age birth.

INTRODUCTION: The 2016 US Surgeon General's Report suggests that the use of electronic nicotine delivery systems (ENDS) is a fetal risk factor. However, no previous study has estimated their effect on adverse pregnancy outcomes. We assessed the prevalence of current ENDS use in pregnant women and explored the effect on birth weight and smallness-for-gestational-age (SGA), correcting for misclassification from nondisclosure of smoking status. METHODS: We conducted a cohort study with 248 pregnant women using questionnaire data and biomarkers (salivary cotinine, exhaled carbon monoxide, and hair nicotine). We evaluated the association between birth weight and the risk of SGA by applying multivariate linear and log-binomial regression to reproductive outcome data for 232 participants. Participants who did not disclose their smoking status were excluded from the referent group. Sensitivity analysis corrected for misclassification of smoking/ENDS use status. RESULTS: The prevalence of current ENDS use among pregnant women was 6.8% (95% CI: 4.4-10.2%); most of these (75%) were concurrent smokers. Using self-reports, the estimated risk ratio of SGA for ENDS users was nearly two times the risk in the unexposed (RR=1.9, 95% CI: 0.6-5.5), and over three times that for ENDS-only users versus the unexposed (RR=3.1, 95% CI: 0.8-11.7). Excluding from the referent group smokers who did not disclose their smoking status, the risk of SGA for ENDS-only use was 5 times the risk in the unexposed (RR=5.1, 95% CI: 1.1- 22.2), and almost four times for all types of ENDS users (RR=3.8, 95% CI: 1.3-11.2). SGA risk ratios for ENDS users, corrected for misclassification due to self-report, were 6.5-8.5 times that of the unexposed. CONCLUSIONS: Our data suggest that ENDS use is associated with an increased risk of SGA.

Testing for treatment effects on gene ontology.

In studies that use DNA arrays to assess changes in gene expression, it is preferable to measure the significance of treatment effects on a group of genes from a pathway or functional category such as gene ontology terms (GO terms, http://www.geneontology.org) because this facilitates the interpretation of effects and may markedly increase significance. A modified meta-analysis method to combine p-values was developed to measure the significance of an overall treatment effect on such functionally-defined groups of genes, taking into account the correlation structure among genes. For hypothesis testing that allows gene expression to change in both directions, p-values are calculated under the null distribution generated by a Monte Carlo method. As a test of this procedure, we attempted to distinguish altered pathways in microarray studies performed with Mitochips, oligonucleotide microarrays specific to mitochondrial DNA-encoded transcripts. We found that our analytic method improves the specificity of selection for altered pathways, due to incorporation of the inter-gene correlation structure in each pathway. It is thus a practical method to measure treatment effects on GO groups. In many actual applications, microarray experiments measure treatment effects under complicated design structures and with small sample sizes. For such applications to real data of limited statistical power, and also in computer simulations, we demonstrate that our method gives reasonable test results.

Simulated solar light-induced p53 mutagenesis in SKH-1 mouse skin: a dose-response assessment.

Sunlight and ultraviolet-induced mutation of the p53 gene is a frequent, possibly obligate step in skin cancer development, making quantitative measurement of p53 mutation an ideal biomarker for sunlight-induced skin carcinogenesis. To understand how the appearance of p53 mutation relates to skin tumor development, SKH-1 hairless mice were exposed 5 d per week to one of four different doses of simulated solar light (SSL; 0, 6.85, 13.70, 20.55 mJ x CIE/cm(2)) previously characterized for their tumorigenic potential. Allele-specific competitive blocker-PCR (ACB-PCR) was used to measure levels of p53 codon 270 CGT to TGT mutation within DNA isolated from dorsal skin of exposed mice. For each dose, p53 mutant fraction (MF) was measured after 4, 16, and 28 wk of exposure. Significant dose- and time-dependent increases in p53 MF were identified. All p53 MF measurements were integrated by relating the observed p53 MF to the cumulative dose of SSL. The increase in the logarithm of p53 MF was described by the linear function: log(10) MF = alpha + 0.0016 x d, where alpha is the spontaneous log(10) MF after a particular time point and d is the dose of SSL in mJ x CIE/cm(2). The p53 MF induced in nontumor bearing skin by 28 wk of exposure at the high dose of SSL was significantly lower than that found in skin tumors induced by approximately 32 wk of exposure to the same dose of SSL. p53 MF showed a strong negative correlation with tumor latency, suggesting this quantitative biomarker has the potential to predict tumorigenicity.