Hormesis and Its Place in Nonmonotonic Dose–Response Relationships: Some Scientific Reality Checks

OBJECTIVE: This analysis is a critical assessment of current hormesis literature. I discuss definitions, characterization, generalizability, mechanisms, absence of empirical data specific for hormesis hypothesis testing, and arguments that hormesis be the “default assumption” in risk assessment. DATA SOURCES: Hormesis, a biological phenomenon typically described as low-dose stimulation from substances producing higher-dose inhibition, has recently garnered interest in several quarters. The principal sources of published materials for this analysis are the writings of certain proponents of hormesis. Surprisingly few systematic critiques of current hormesis literature exist. Limits to the phenomenon’s appropriate role in risk assessment and health policy have been published. DATA SYNTHESIS: Serious gaps in scientific understanding remain: a stable definition; generalizability, especially for humans; a clear mechanistic basis; limitations in the presence of multiple toxic end points, target organs, and mechanisms. Absence of both arms-length, consensus-driven, scientific evaluations and empirical data from studies specifically designed for hormesis testing have limited its acceptance. CONCLUSIONS: Definition, characterization, occurrence, and mechanistic rationale for hormesis will remain speculative, absent rigorous studies done specifically for hormesis testing. Any role for hormesis in current risk assessment and regulatory policies for toxics remains to be determined

Peer Helping in an Intercollegiate Athletic Environment

Intercollegiate student-athletes face a variety of unique responsibilities and stressors. Balancing practice, training, traveling, and academics can be overwhelming. To assist student-athletes with these issues, the peer helper program called the Student Peer Athlete Network (SPAN) was developed. SPAN was designed to train specific student-athletes in peer helper skills so they, in turn, can assist other student-athletes who need support or assistance for certain personal, academic, or athletic concerns. Empowering student-athletes promotes a sense a self-responsibility and benefits the entire student-athlete population

A Comprehensive Education and Prevention Program for Student-Athletes: A Life Skills/Experiential Learning Model

The purpose of this longitudinal drug prevention program sponsored by the NCAA was to provide a unique experiential learning approach for student-athletes. Data were obtained from freshman student-athletes before and after a fall semester drug education course via a questionnaire measuring self-esteem, knowledge, attitudes, frequency of usage, risk factors, and demographic variables. In this program, freshman student-athletes were required to enroll in a one-credit health education "Values and Health" course during the fall semester. Topics included stress management skills, sports nutrition, eating disorders, sexuality, date rape, and, most importantly, five session on alcohol use and abuse. The authors collecgted 158 freshman drug questionnaires prior to the start of the program, and collected 43 post-tests after the course for matched data. They also collected data from 33 senior track athletes. For a control group, they also surveyed 60 club sport athletes and 87 non-athletes. The data for all groups was the Student-Athlete Service Questionnaire which included questions from the Rosenberg Self-Esteem Scale. MANOVAs were computed for four dependent measures (self-esteem, knowledge, attitude, and risk factors) and independent variables (drug user/non-user, subject sex, sprot type, parental income cateogry, financial aid status, and time) were examined for each drug category. The effectiveness of the freshman program was analyzed, and further comparisons were made with other student-athlete and non-athlete groups. Alcohol was found to be the most widely used drug, while use of performance and societal drugs was extremely low. The freshman program was found to have a significant impact on enhancing drug knowledge, as findings indicated freshman athletes (especially in non-contact sports) are at a higher risk for recreational drug use than other athletes and non-athletes. Additional multivariate analyses examined other attitudinal and psychological variables

Genetic integrity of the human Y chromosome exposed to groundwater arsenic

<p>Abstract</p> <p>Background</p> <p>Arsenic is a known human carcinogen reported to cause chromosomal deletions and genetic anomalies in cultured cells. The vast human population inhabiting the Ganges delta in West Bengal, India and Bangladesh is exposed to critical levels of arsenic present in the groundwater. The genetic and physiological mechanism of arsenic toxicity in the human body is yet to be fully established. In addition, lack of animal models has made work on this line even more challenging.</p> <p>Methods</p> <p>Human male blood samples were collected with their informed consent from 5 districts in West Bengal having groundwater arsenic level more than 50 μg/L. Isolation of genomic DNA and preparation of metaphase chromosomes was done using standard protocols. End point PCR was performed for established sequence tagged sites to ascertain the status of recombination events. Single nucleotide variants of candidate genes and amplicons were carried out using appropriate restriction enzymes. The copy number of DYZ1 array per haploid genome was calculated using real time PCR and its chromosomal localization was done by fluorescence in-situ hybridization (FISH).</p> <p>Results</p> <p>We studied effects of arsenic exposure on the human Y chromosome in males from different areas of West Bengal focusing on known recombination events (P5-P1 proximal; P5-P1 distal; gr/gr; TSPY-TSPY, b1/b3 and b2/b3), single nucleotide variants (SNVs) of a few candidate Y-linked genes (DAZ, TTY4, BPY2, GOLGA2LY) and the amplicons of AZFc region. Also, possible chromosomal reorganization of DYZ1 repeat arrays was analyzed. Barring a few microdeletions, no major changes were detected in blood DNA samples. SNV analysis showed a difference in some alleles. Similarly, DYZ1 arrays signals detected by FISH were found to be affected in some males.</p> <p>Conclusions</p> <p>Our Y chromosome analysis suggests that the same is protected from the effects of arsenic by some unknown mechanisms maintaining its structural and functional integrities. Thus, arsenic effects on the human body seem to be different compared to that on the cultured cells.</p

Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells

Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl2 and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl2 concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis