title: Carcinogen-DNA adducts and gene mutation in foundry workers with low-level exposure to polycyclic aromatic hydrocarbons.
abstract: 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[a]P exposure declined by approximately 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 < or = 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 half-life on the order of several months) were markedly reduced from the first to the second year (PAH-DNA, 6.2 versus 2.3/10(8); aromatic-DNA, 2.5 versus 1.4/(8); P < 0.01). HPRT Mf (a longer-lived marker) was somewhat less affected by the decline in exposure (1.3 versus 0.8, P < or = 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.
authors.affiliation: Columbia University, New York, NY 10032.
authors.forename: F P
authors.initials: FP
authors.lastname: Perera
authors.forename: C
authors.initials: C
authors.lastname: Dickey
authors.forename: R
authors.initials: R
authors.lastname: Santella
authors.forename: J P
authors.initials: JP
authors.lastname: O'Neill
authors.forename: R J
authors.initials: RJ
authors.lastname: Albertini
authors.forename: R
authors.initials: R
authors.lastname: Ottman
authors.forename: W Y
authors.initials: WY
authors.lastname: Tsai
authors.forename: L A
authors.initials: LA
authors.lastname: Mooney
authors.forename: K
authors.initials: K
authors.lastname: Savela
authors.forename: K
authors.initials: K
authors.lastname: Hemminki
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis; D000328:Adult; D000368:Aged; D001564:Benzo(a)pyrene / Q000009:adverse effects; D015415:Biomarkers; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000187:drug effects / Q000235:genetics; D018736:DNA Adducts / Q000032:analysis / Q000737:chemistry; D004249:DNA Damage; D005260:Female; D005387:Finland; D005796:Genes / Q000187:drug effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007501:Iron; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008669:Metallurgy; D008875:Middle Aged; D016296:Mutagenesis; D016273:Occupational Exposure; D011083:Polycyclic Compounds / Q000009:adverse effects*; D018570:Risk Assessment; D012907:Smoking
chemical_list: D015415:Biomarkers; D018736:DNA Adducts; D011083:Polycyclic Compounds; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; D007501:Iron; D007041:Hypoxanthine Phosphoribosyltransferase