TY - JOUR
T1 - Carcinogen-DNA adducts and gene mutation in foundry workers with low-level exposure to polycyclic aromatic hydrocarbons
AU - Perera, R. R.
AU - Dickey, C.
AU - Santella, R.
AU - O'neill, J. P.
AU - Albertini, R. J.
AU - Ottman, R.
AU - Tsai, W. Y.
AU - Mooney, L. A.
AU - Savela, K.
AU - Hemminki, K.
N1 - Funding Information:
We thank T.L.Young, L.W.Wang, LJ^.Sullivan, B.A.Nisbet and A.E.Gorvard for technical assistance in the laboratory. This work was supported by NIEHS grant 1-P01-E505249, American Cancer Society SIG-13, the Lucille M.Markey Charitable Trust, the Swedish Work Environment Fund and the Bauman Foundation.
PY - 1994/12
Y1 - 1994/12
N2 - Carcinogen-DNA adducts and somatic gene mutation at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus were evaluated in peripheral leukocytes of workers in an iron foundry with exposure to benzo[a]pyrene (B[a]P) and other polycyclic aromatic hydrocarbons (PAHs). During the two year study period, B[α]P exposure declined by ∼40%, from a maximum of 60 ng/m3 in the first year to <36 ng/m3 1 year later. A total of 64 persons were sampled in November/December of the two successive study years; 24 of them gave two samples one year apart. The biomarkers included carcinogen-DNA adducts in leukocytes (PAH-DNA measured by an immunoassay, aromatic-DNA by the 32P-postlabeling method) and HPRT mutation in lymphocytes. After adjusting for smoking, levels of PAH-DNA, aromatic-DNA and HPRT mutation frequency (Mf) increased with exposure among the 64 workers sampled during the 2 year period (P ≤ 0.05). However, the markers showed a differential response to the change in exposure, consistent with their individual biology. For example, among the 24 workers sampled in both years, carcinogen-DNA adducts (which have a halflife on the order of several months) were markedly reduced from the first to the second year (PAH-DNA, 6.2 versus 2.3/108; aromatic-DNA, 2.5 versus 1.4/108; P <0.01). HPRT Mf (a longer-lived marker) was somewhat less affected by the decline in exposure (13 versus 0.8, P < 0.05). Moreover, in the second year several long-term workers had low levels of adducts, but elevated HPRT Mf. Thus, PAH-DNA and HPRT Mf were highly correlated in the first year (n = 17; r = 0.67;P <0.01), but not in the second year or in the two years combined. However, when analysis was restricted to workers with detectable levels of adducts (who included the more highly exposed workers) the correlation was significant between PAH-DNA and HPRT (n = 17; r = 0.65; P = 0.005). In contrast, aromatic-DNA adducts and HPRT were not correlated in either year. These results suggest a molecular link between somatic gene mutation and PAHs; and they highlight the need in such molecular epidemiologic studies to consider the varying lifetimes of the individual markers.
AB - Carcinogen-DNA adducts and somatic gene mutation at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus were evaluated in peripheral leukocytes of workers in an iron foundry with exposure to benzo[a]pyrene (B[a]P) and other polycyclic aromatic hydrocarbons (PAHs). During the two year study period, B[α]P exposure declined by ∼40%, from a maximum of 60 ng/m3 in the first year to <36 ng/m3 1 year later. A total of 64 persons were sampled in November/December of the two successive study years; 24 of them gave two samples one year apart. The biomarkers included carcinogen-DNA adducts in leukocytes (PAH-DNA measured by an immunoassay, aromatic-DNA by the 32P-postlabeling method) and HPRT mutation in lymphocytes. After adjusting for smoking, levels of PAH-DNA, aromatic-DNA and HPRT mutation frequency (Mf) increased with exposure among the 64 workers sampled during the 2 year period (P ≤ 0.05). However, the markers showed a differential response to the change in exposure, consistent with their individual biology. For example, among the 24 workers sampled in both years, carcinogen-DNA adducts (which have a halflife on the order of several months) were markedly reduced from the first to the second year (PAH-DNA, 6.2 versus 2.3/108; aromatic-DNA, 2.5 versus 1.4/108; P <0.01). HPRT Mf (a longer-lived marker) was somewhat less affected by the decline in exposure (13 versus 0.8, P < 0.05). Moreover, in the second year several long-term workers had low levels of adducts, but elevated HPRT Mf. Thus, PAH-DNA and HPRT Mf were highly correlated in the first year (n = 17; r = 0.67;P <0.01), but not in the second year or in the two years combined. However, when analysis was restricted to workers with detectable levels of adducts (who included the more highly exposed workers) the correlation was significant between PAH-DNA and HPRT (n = 17; r = 0.65; P = 0.005). In contrast, aromatic-DNA adducts and HPRT were not correlated in either year. These results suggest a molecular link between somatic gene mutation and PAHs; and they highlight the need in such molecular epidemiologic studies to consider the varying lifetimes of the individual markers.
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U2 - 10.1093/carcin/15.12.2905
DO - 10.1093/carcin/15.12.2905
M3 - Article
C2 - 8001254
AN - SCOPUS:0028567143
SN - 0143-3334
VL - 15
SP - 2905
EP - 2910
JO - Carcinogenesis
JF - Carcinogenesis
IS - 12
ER -