Airway Genetics and Ambient Combustion Aerosol

SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?

SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?

Links: 35 CAR Test SPC Questions
CAR Warm Up
SPC 1 Introduction: South Pole CAR (SPC) - A Character Test
SPC 2 South Pole CAR: ACA PM, Band Cell, and Monocyte Drop
SPC 3 ACA PM and ME/CFS: Do We Hear An Echo?
SPC 4 ACA UFPM: In the RBC - Through the BBB
SPC 5 ACA UFPM: IL-1 beta, RBC, BBB, - MCS and ME/CFS
SPC 6 ACA UFPM: Nerve Penetration
SPC 7 ACA UFPM: Olfactory, BBB, AD, PD, MCS, and ME/CFS
SPC 8 ACA PM: Gastro-Inflammation, Immunity, Vagal Circuitry
SPC 9 Veronesi: Sensory Nerve Insight
SPC 10 Kimata: Histamine Warning - Return to Masking
SPC 11 Central Sensitization: Intense, Repeated, and Sustained Inputs

On CAR
SPC 12 Disease Conditions Begin: Airway Epithelial Injury
SPC 13 Exposed Sensory Nerves - TRPA1
SPC 14 Exposed TRPA1: Central Sensitization
SPC 15 ACA: Loud and Clear
SPC 16 Airway Cytokine Release: Principle Mediator of Systemic Inflammation
SPC 17 Calderon-Garciduenas: Airway to Systemic: Putting It Together
SPC 18 Airway Gaps - Exposed Nerves - UFPM to the CNS
SPC 19 ACA PM: Months and Years Residence Time
SPC 20 Airway Gaps: Reduced Detox Enzyme Intervention
SPC 21 Solvents and Pesticides Primary: Shoe Fits Glove?
SPC 22 Veronesi and Roy: Genetic Difference in Airway Sensitivity

SPC 23 Jung Was Right Sort Of

SPC 24 Veronesi and Jung: A Perfect Match
SPC 25 Tailpipe and Chimney Emissions: Horizontal Coning
SPC 26 How Far Symptoms Travel: 25 Years, 500 Locations, 22 States
SPC 27 Not Into That Kind of Entertaining
SPC 28 Does it Cost More Than Money?
SPC 29 Airway to Systemic: Dysfunction of Detox Enzymes - Terlecky
SPC 30 Airway to systemic: Dysfunction of Detox Enzymes - Khatsenko
SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?
SPC 32 Phase I and II Detox Enzymes Defined

Lifestyle Change
SPC 33 ACA Catastrophic Consequences
SPC 34 Impossibly Good City Design
SPC 35 South Pole CAR Test: Satisfaction Guarantee

MCS 3 Definition and Concensus Criteria

MCS 3a Criteria Amendment Research Points (CAR)

MCS 3aa Etiology: Concensus Author CAR Test (SPC)

MCS 3b CAR References

SPC 31 Gerde and Stadler: Benzo[a]pyrene Forever?

Please choose the Incorrect Statement

SPS 31a)

BAULIG 2009:

"...particulate matter is a very complex mixture containing various components such as carbonaceous core, polyaromatic hydrocarbons (PAH), quinones, metals, endotoxins, and many other components (Harrison and Yin 2000)..."

SPC 31b)

GERDE 2001:

During combustion particles are generated and PAHs (polycyclic aromatic hydrocarbons) form in the gas phase. When the exhaust cools - PAHs adsorb or condense on the particles (Burtscher 1998).

There are two principal fractions of adsorbed PAHs: one is quickly desorbed - and the other retained on particles for a long time (Gerde 1991, Burtscher 1986, Adamson 1982, Natusch 1978).
Approx 80% of rapidly desorbed PAHS are deposited on the thin alveolar type 1 epithelium deep in the lung (Yeh 1996) and become systemic quickly with blood concentration peaking in several minutes.
3/4 of blood activity from the rapidly absorbed B[a]P (benzo[a]pyrene) used in Gerde 2001 ceased in 10 minutes - nearly all within 30 - and by one hour completely leveled - mostly into conjugated phase ll metabolites (Fung 1999, Thompson 1989, Molliere 1987).
In contrast, the remaining 20% of rapidly desorbed PAHs "...are deposited, slowly absorbed, and extensively metabolized in airway epithelium at prolonged elevation of the local tissue concentration (Gerde 1997)..."
Over 5 months later particles in the lung and lymph nodes had only 37 and 59% of B[a]P desorbed - mostly during the initial rapid release - with the exception of more desorption from particles translocated to the lymph nodes - possibly due to environment within macrophages (Nyberg 1989, Harmsen 1985 , Lundborg 1984).

SPC 31c)

BAULIG 2003a:

"...In airway epithelial cells, DEP (diesel exhaust particles) via their organic components (polycyclic aromatic hydrocarbons PAHs including benzo[a]pyrene desorbed from the carbonaceous core), modify the cellular redox state...induce phase I (CYP1A1) and phase II (NQO-1) gene expression and can be metabolized,,,numerous genes implicated in detoxification...activated via xenobiotic responsive element and ARE (antioxidant responsive element) as well as in the secretion of proinflammatory cytokines via NFkB responsive element (Bonvallot 2001)..."

SPC 31d)

DELUCA 2010:

"...Notwithstanding the absence of genetic defects in CYPs, recent studies have increasingly implicated various inflammatory stimuli, first of all, pro-inflammatory cytokines (Chun 2002, Nadin 1995, Tapner 1996, Tinel 1999) to cause changes in the activities and expression levels of CYPs through nitric oxide signalling (Chun 2002, Stadler 1994). For example, drug metabolizing CYPs such as CYP3A4 and CYP2B6, which are constitutively expressed in human mono nuclear cells, have been significantly repressed by IFN Gamma or IL-2 (Liptrott 2009)...

Our results suggest that serious and multiple dysfunctions of chemical defense systems found in MCS patients may mainly not depend on genetic defects, but instead may rely on non-genetic modifications of metabolizing/antioxidant enzyme expression and/or activity, mediated by redox active agents such as NO and inflammatory cytokines..."Found elevated in MCS patients (Dantoft 2014, Deluca 2010)

"...Dysfunction of two major antioxidant enzymes and depletion of glutathione inevitably leads to severe oxidative stress and impaired elimination of phase 1 oxidation metabolites. Excessive amounts of hydrogen peroxide due to catalase deficiency will initiate a non enzymatic free radical driven chain reaction of lipid peroxidation implicated in a number of human pathologies..."

SPC 31e)

STADLER 1994:
"...Inflammatory stimulation of the liver leads to the induction of nitric oxide (NO) biosynthesis. Because NO binds to the catalytic heme moiety of cytochromes P450 (CYPs), we investigated whether NO interferes with specific CYP-dependent metabolic pathways...
...NO synthesis was induced in rat hepatocytes by incubation with a mixture of cytokines and endotoxin. Concurrently, as NO production in hepatocytes increased within 24 hr, a decrease in CYP1A1 dependent benzo[a]pyrene turnover was observed to almost undetectable levels...the inhibition of benzo[a]pyrene turnover by endogenous NO must have been predominantly due to functional inhibition of CYP activity...
...Inhibition of hepatocellular CYP activity by NO was predominantly due to a direct effect on the enzymes. However, NO-dependent inhibition of CYP expression at a transcriptional level was also demonstrated..."

SPC 31f)
PM induced cytokine release and NO production - inflammatory stimulation - cannot inhibit CYP activity - dysfunction of xenobiotic metabolizing enzymes - as shown by Stadler 1994 and others (Deluca 2010, Liptrott 2009, Oslund 2008, Chun 2002, Sterner-Kock 1999, Tinel 1999, Tanabe 1996, Tapner 1996, Nadin 1995, Khatsenko 1993).