Variability in PAH-DNA adduct measurements in peripheral mononuclear cells: Implications for quantitative cancer risk assessment

Chris Dickey, Regina M. Santella, Dale Hattis, Deliang Tang, Yanzhi Hsu, Tom Cooper, Tie L. Young, Frederica P. Perera

Research output: Contribution to journalArticle

Abstract

Biomarkers such as DNA adducts have significant potential to improve quantitative risk assessment by characterizing individual differences in metabolism of genotoxins and DNA repair and accounting for some of the factors that could affect interindividual variation in cancer risk. Inherent uncertainty in laboratory measurements and within-person variability of DNA adduct levels over time are putatively unrelated to cancer risk and should be subtracted from observed variation to better estimate interindividual variability of response to carcinogen exposure. A total of 41 volunteers, both smokers and nonsmokers, were asked to provide a peripheral blood sample every 3 weeks for several months in order to specifically assess intraindividual variability of polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels. The intraindividual variance in PAH-DNA adduct levels, together with measurement uncertainty (laboratory variability and unaccounted for differences in exposure), constituted roughly 30% of the overall variance. An estimated 70% of the total variance was contributed by interindividual variability and is probably representative of the true biologic variability of response to carcinogenic exposure in lymphocytes. The estimated interindividual variability in DNA damage after subtracting intraindividual variability and measurement uncertainty was 24-fold. Inter- individual variance was higher (52-fold) in persons who constitutively lack the Glutathione S-Transferase M1 (GSTM1) gene which is important in the detoxification pathway of PAH. Risk assessment models that do not consider the variability of susceptibility to DNA damage following carcinogen exposure may underestimate risks to the general population, especially for those people who are most vulnerable.

Original languageEnglish (US)
Pages (from-to)649-656
Number of pages8
JournalRisk Analysis
Volume17
Issue number5
StatePublished - Oct 1997

Fingerprint

Polycyclic aromatic hydrocarbons
Risk assessment
risk assessment
Uncertainty
cancer
DNA Adducts
Carcinogens
DNA Damage
DNA
Neoplasms
Polycyclic Aromatic Hydrocarbons
Mutagens
Individuality
DNA Repair
Detoxification
Lymphocytes
Volunteers
Biomarkers
Metabolism
uncertainty

Keywords

  • PAH-DNA adducts
  • Risk assessment
  • Uncertainty
  • Variability

ASJC Scopus subject areas

  • Safety, Risk, Reliability and Quality
  • Social Sciences (miscellaneous)

Cite this

Dickey, C., Santella, R. M., Hattis, D., Tang, D., Hsu, Y., Cooper, T., ... Perera, F. P. (1997). Variability in PAH-DNA adduct measurements in peripheral mononuclear cells: Implications for quantitative cancer risk assessment. Risk Analysis, 17(5), 649-656.

Variability in PAH-DNA adduct measurements in peripheral mononuclear cells : Implications for quantitative cancer risk assessment. / Dickey, Chris; Santella, Regina M.; Hattis, Dale; Tang, Deliang; Hsu, Yanzhi; Cooper, Tom; Young, Tie L.; Perera, Frederica P.

In: Risk Analysis, Vol. 17, No. 5, 10.1997, p. 649-656.

Research output: Contribution to journalArticle

Dickey, C, Santella, RM, Hattis, D, Tang, D, Hsu, Y, Cooper, T, Young, TL & Perera, FP 1997, 'Variability in PAH-DNA adduct measurements in peripheral mononuclear cells: Implications for quantitative cancer risk assessment', Risk Analysis, vol. 17, no. 5, pp. 649-656.
Dickey, Chris ; Santella, Regina M. ; Hattis, Dale ; Tang, Deliang ; Hsu, Yanzhi ; Cooper, Tom ; Young, Tie L. ; Perera, Frederica P. / Variability in PAH-DNA adduct measurements in peripheral mononuclear cells : Implications for quantitative cancer risk assessment. In: Risk Analysis. 1997 ; Vol. 17, No. 5. pp. 649-656.
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