Tumor promoting properties of a cigarette smoke prevalent polycyclic aromatic hydrocarbon as indicated by the inhibition of gap junctional intercellular communication via phosphatidylcholine-specific phospholipase C

Inhibition of gap junctional intercellular communication (GJIC) and the activation of intracellular mitogenic pathways are common hallmarks of epithelial derived cancer cells. We previously determined that the 1-methyl and not the 2-methyl isomer of anthracene, which are prominent cigarette smoke components, activated extracellular receptor kinase, and inhibited GJIC in WB-F344 rat liver epithelial cells. Using these same cells, we show that an immediate upstream response to 1-methylanthracene was a rapid ( LT 1 min) release of arachidonic acid. Inhibition of phosphatidylcholine-specific phospholipase C prevented the inhibition of GJIC by 1-methylanthracene. In contrast, inhibition of phosphatidylinositol specific phospholipase C, phospholipase A(2), diacylglycerol lipase, phospholipase D, protein kinase C, and tyrosine protein kinases had no effect on 1-methylanthracene-induced inhibition of GJIC. Inhibition of protein kinase A also prevented inhibition of GJIC by 1-methylanthracene. Direct measurement of phosphatidylcholine-specific phospholipase C and sphingomyelinase indicated that only phosphatidylcholine-specific phospholipase C was activated in response to 1-methylanthracene, while 2-methylanthracene had no effect. 1-methylanthracene also activated p38-mitogen activated protein kinase; however, like extracellular kinase, its activation was not involved in 1-methylanthracene-induced regulation of GJIC, and this activation was independent of phosphatidylcholine-specific phospholipase C. Although mitogen activated protein kinases were activated, Western blot analyzes indicated no change in connexin43 phosphorylation status. Our results indicate that phosphatidylcholine-specific phospholipase C is an important enzyme in the induction of a tumorigenic phenotype, namely the inhibition of GJIC; whereas mitogen activated protein kinases triggered in response to 1-methylanthracene, were not involved in the deregulation of GJIC

Reasons for non-participation of children and adolescents in a large-scale school-based mental health project.

BACKGROUND Non-participation in mental health studies is an under-explored but very important topic. Investigating reasons for non-participation holds promise for the planning of future study designs and recruitment strategies. This study aimed at investigating reasons for children and adolescents (C&A) not participating in a school-based mental health research project. METHODS Data collection took place within the school-based recruitment of a large-scale multi-site project ("ProHEAD-Promoting Help-seeking using E-technology for Adolescents") in Germany. Participants were N = 534 C&A aged ≥ 12 years attending secondary schools. The present cross-sectional study analyzed anonymous survey data of C&A who themselves or whose parents, respectively, did not provide written consent to participate in the mental health research project. The questionnaire consisted of 14 items covering potential reasons for non-participation, and four free text fields. Besides descriptive statistics, free text field answers were analyzed using qualitative content analysis. RESULTS Students indicated an average of M = 2.94 (SD = 1.75) reasons for their non-participation in the project. In the descriptive analysis of indicated items, the three most frequently reported reasons for non-participation included students reporting to not be concerned by the topic "mental health" (n = 290, 54.3%), not having returned the consent form to the teacher (n = 175, 32.8%), and not having time for participation (n = 149, 27.9%). In the qualitative content analysis, the most frequently assigned categories were organizational reasons (n = 216, 57.1%), general disinterest in study participation (n = 139, 36.8%), and personal attitudes toward the topic "mental health" (n = 84, 22.2%), such as not being concerned with the topic "mental health" (n = 23, 6.1%) or being too concerned with the topic "mental health" (n = 16, 4.2%). CONCLUSION The study provides unique insights into reasons for C&A and their caregivers not participating in a large federally funded mental health research project. The results suggest that in order to increase participation rates, stigma should be reduced, parents as well as teachers should be involved where possible, and the use of incentives might be helpful. The study highlights the importance of assessing reasons for non-participation, especially in online intervention studies on mental health