Effects of combined superoxide dismutase and catalase on somatosensory evoked potentials and neuropathologic changes in asphyxiated newborn lambs.

The lamb model of neonatal asphyxia has been used to describe changes in cerebral blood flow, oxygen metabolism and mitochondrial function following a standard asphyxial insult. In addition, abnormalities in cerebral hemodynamics and mitochondrial function after asphyxia have been associated with injury mediated by oxygen free radicals. The purpose of this investigation was to describe changes in brainstem auditory and somatosensory evoked potentials and pathologic changes after asphyxia in the newborn lamb.

Family history of cancer, mutagen sensitivity, and increased risk of head and neck cancer.

To evaluate individual cancer susceptibility, 170 previously untreated patients with pathologically-confirmed squamous cell carcinoma of the oral cavity, pharynx, and larynx, and 175 age- and sex-matched health controls were investigated for the occurrence of cancer in first-degree relatives along with other established risk factors for head and neck cancer. More than 54% of these subjects were assayed for mutagen sensitivity by quantifying in-vitro bleomycin-induced chromosomal breaks within peripheral blood lymphocytes. After adjusting for age, gender, education, family income, tobacco and alcohol consumption, the odds ratio associated with three or more first-degree relatives with cancer at any site was 3.

Analysis of aromatic DNA adducts and 7,8-dihydro-8-oxo- 2'-deoxyguanosine in lymphocyte DNA from a case-control study of lung cancer involving minority populations.

The purpose of this study was to examine the level of smoking-related aromatic DNA adducts and oxidative DNA damage in current smokers from a lung cancer case-control study in African Americans and Mexican Americans. In addition, mutagen sensitivity (bleomycin-induced chromatid breaks), a marker of genetic susceptibility, was assessed in these patients and correlated with the level of DNA damage. Lymphocyte DNA from cases and age-, sex-, and ethnicity-matched controls was analyzed for aromatic DNA adducts (43 cases and 47 controls) and the level of 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was determined in 46 cases and 48 controls using (32)P-postlabeling.

Marijuana use and increased risk of squamous cell carcinoma of the head and neck.

Marijuana is the most commonly used illegal drug in the United States. In some subcultures, it is widely perceived to be harmless. Although the carcinogenic properties of marijuana smoke are similar to those of tobacco, no epidemiological studies of the relationship between marijuana use and head and neck cancer have been published.

Limiting the location of a putative human prostate cancer tumor suppressor gene at chromosome 13q14.3.

We studied loss of heterozygosity (LOH) on human chromosome 13q in prostate cancer specimens to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the clinicopathological stage of the disease. Overall 13 (21%) of 61 specimens analysed had an allele loss on the long arm of chromosome 13. The most frequent (37%) LOH among the informative cases with allele losses was detected at the D13S284 locus on chromosome 13q14.

Genetic susceptibility to tobacco carcinogenesis.

Lung cancer risk is thus defined by the balance between metabolic activation and detoxification of xenobiotic compounds and by the efficiency of DNA repair. It is most likely that multiple susceptibility factors must be accounted for to represent the true dimensions of gene-environment interactions. The ability to identify smokers with the highest risks of developing cancer has substantial preventive implications.

Polymorphisms of DNA repair gene XRCC1 in squamous cell carcinoma of the head and neck.

Because reduced DNA repair capacity (phenotype) has been suggested as a risk factor for squamous cell carcinoma of the head and neck (SCCHN), newly-identified DNA repair gene polymorphisms (genotype) may also be implicated in risk. To test this hypothesis, we conducted a case-control study of 203 SCCHN patients and 424 control subjects (matched for age, sex and ethnicity) to investigate the role of two XRCC1 polymorphisms (XRCC1 26304 T and XRCC1 28152 A, respectively) in SCCHN. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (CI).

Ethnic differences in poly(ADP-ribose) polymerase pseudogene genotype distribution and association with lung cancer risk.

Poly(ADP-ribose) polymerase (PADPRP) is a nuclear DNA-binding enzyme that can modulate chromatin structure close to DNA replication, recombination and repair regions. Two-allele polymorphism on the PADPRP chromosome 13 pseudogene has been studied in several ethnic subpopulations, and the association of each allele with different types of cancer has been investigated. To study the frequency of the allele in the context of lung cancer, we performed a PCR assay for the PADPRP polymorphism in 288 lung cancer patients and 292 matched controls and examined the frequency of the alleles in different ethnic groups.

Associations among telomerase activity, p53 protein overexpression, and genetic instability in lung cancer.

Genomic instability is a driving force for tumorigenesis. p53 and telomerase play central roles in maintaining genomic integrity. The purpose of this study was to assess the associations among p53 protein overexpression, telomerase activity and genetic instability in lung cancer.

Glutathione-S-transferase polymorphisms and risk of squamous-cell carcinoma of the head and neck.

Differences in genetic susceptibility to tobacco-induced carcinogenesis appear to modulate an individual's risk of squamous-cell carcinoma of the head and neck (SCCHN). Risk for SCCHN may be associated with the null alleles of the carcinogen-metabolizing genes glutathione-S-transferase (GST) T1 and GSTM1. In this study, we evaluated the association between GSTM1 and GSTT1 null genotypes and risk of SCCHN in a matched case-control study of 162 patients with SCCHN and 315 healthy controls.

Is there a genetic basis for lung cancer susceptibility?

The major risk factor for lung cancer is exposure to tobacco smoke. Exposure to radon, heavy metals used in smelting, and asbestos also greatly increase risks for lung cancer. However, only about 11% of tobacco smokers ultimately develop lung cancer, suggesting that genetic factors may influence the risk for lung cancer among those who are exposed to carcinogens.

Phytoestrogen intake and prostate cancer: a case-control study using a new database.

In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls.

Development of a database for assessing dietary phytoestrogen intake.

For the past two decades, epidemiologists have observed lower risks of lung, breast, prostate, colon, and other cancers in populations that frequently consume fruits and vegetables. Numerous phytoestrogens have been shown to be anticarcinogenic under experimental conditions and may account for at least part of the cancer-prevention effects of fruit and vegetable consumption. These plant constituents include isoflavonoids, coumestans, lignans, phytosterols, and flavonoids.

Three measures of mutagen sensitivity in a cancer-free population.

Different individuals appear to respond differently to the same carcinogen, and different mutagens act differently on cells. We conducted mutagen sensitivity assays by using three mutagens (bleomycin, a radiomimetic agent; 4-nitroquinoline-1-oxide [4-NQO], an ultraviolet light mimetic agent; and benzo[a]pyrene diol epoxide [BPDE], a tobacco mutagen) in parallel in healthy human subjects to determine the relationships among these assays. Our results showed that the mean breaks per cell values (b/c) (+/- SD) for bleomycin, 4-NQO, and BPDE sensitivity were 0.

Case-control study of diet and prostate cancer in China.

Introduction: A higher incidence of prostate cancer is observed in the Western world than in Asian countries. Although it is relatively rare in China, an increased incidence has been reported in recent years. Studies in high-risk populations have suggested that dietary fat may play a role in enhancing the risk of developing prostate cancer.

Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis.

Background: Insulin-like growth factors (IGFs), in particular IGF-I and IGF-II, strongly stimulate the proliferation of a variety of cancer cells, including those from lung cancer. To examine the possible causal role of IGFs in lung cancer development, we compared plasma levels of IGF-I, IGF-II, and an IGF-binding protein (IGFBP-3) in patients with newly diagnosed lung cancer and in control subjects.

Methods: From an ongoing hospital-based, case-control study, we selected 204 consecutive patients with histologically confirmed, primary lung cancer and 218 control subjects who were matched to the case patients by age, sex, race, and smoking status.

Chromosome 5 aberrations and genetic predisposition to lung cancer.

In this study, we aimed to confirm the finding that chromosome 5 aberrations are predisposing factors for lung cancer. The study population consisted of 118 previously untreated lung cancer patients and 101 healthy controls. Lymphocytes were treated with bleomycin for 5 hr and then allowed to recover in a drug-free medium for 48 hr.

Benzo[a]pyrene diol epoxide and bleomycin sensitivity and susceptibility to cancer of upper aerodigestive tract.

Background: Tobacco smoking is an established risk factor for cancers of the upper aerodigestive tract, and measurement of chromosomal aberrations, i.e., chromatid breaks, induced in lymphocytes in vitro by bleomycin has been shown to be a predictor of risk for these cancers.

A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and controls.

Background: Because only a fraction of smokers develop neoplastic lesions, host factors may affect their susceptibility to the carcinogenic effects of tobacco smoke. Benzo[a]pyrene diol epoxide (BPDE) is the metabolic product of benzo[a]pyrene (B[a]P), a constituent of tobacco smoke. Therefore, BPDE sensitivity may shed some light on smoking-related carcinogenesis.

Mutagen sensitivity as a susceptibility marker for human hepatocellular carcinoma.

Although the pathogenesis of hepatocellular carcinoma (HCC) remains poorly understood, hepatitis B virus and dietary aflatoxin exposures are established etiological factors for this disease. We conducted a pilot study of 28 patients with HCC and 110 healthy controls matched for age, sex, and ethnicity to determine whether constitutional genetic instability, based on the quantification of mutagen-induced chromatid breaks in cultured lymphocytes, modifies an individual's risk of HCC development. The mean numbers of bleomycin-induced breaks per cell for cases and controls were 0.

Mutagen sensitivity to benzo(a)pyrene diol epoxide and the risk of squamous cell carcinoma of the head and neck.

Genetic susceptibility appears to modulate an individual's risk of tobacco-induced carcinoma. One biomarker of such susceptibility, chromatid breaks induced in vitro in lymphocytes by the mutagen bleomycin, is an independent risk factor for several malignancies. To date, the more etiologically appropriate mutagen benzo(a)pyrene diol epoxide (BPDE) has only been used in one lung cancer study.