Interception of reactive, DNA adduct-forming metabolites present in rodent serum following carcinogen exposure: Implications for use of body fluids in biomonitoring (original) (raw)

1993, Teratogenesis, Carcinogenesis, and Mutagenesis

The detection of adduct-forming metabolites in the serum of carcinogen treated animals by 32P-postlabeling was evaluated as a novel approach to overcome the stringent requirement of obtaining DNA from tissues in human biomonitoring assessments. Benzo[a]pyrene(BP) was giveni.p. to B6C3Fi, C57B1/6, ICR, andDBAI2mousestrains as well as Sprague-Dawley rats. Three adducts related to BP were detected in the liver and/or lung of Sprague-Dawley rats or B6C3F1, C57BU6, and ICR mice; a single adduct was detected in the liver and lung of the DBAI2 mouse strain. Adducts chromatographically similar to those found in these tissues were also detected when salmon sperm DNA was incubated with the serum of BP-treated animals. Benzidine treatment induced the formation of one adduct in the liver of B6C3F1 mice, which was chromatographically similar to dG-C8-N'-acetylbenzidine. An identical adduct was detected in the salmon sperm DNA incubated with the serum of these mice. Cyclopenta[cd]pyrene treatment produced four major and three minor adducts in the liver or lung of B6C3Ft mice, all but two of which were detected in DNA incubated with serum of cyclopenta[cd]pyrenetreated animals. Large interstrain differences in the serum level of BP adduct-forming metabolites as well as tissue DNA adducts were found which correlated with previously observed strain-specific trends in sensitivity to PAH-mediated carcinogenesis. Thus, levels of BP adduct-forming metabolites were found in the following descending order: B6C3F1, C57B1/6, ICR, and DBA/2. BP-derived adduct-forming metabolites were detectable as late as 2 d and 5 d post-treatment in the serum of C57B116 mice or Sprague-Dawley rats, respectively, which seems to coincide well with the reported species-specific turnover of serum albumin; aprotein know to be involved in the transport Address reprint requests to Ramesh CAbbreviations: PAH, polycyclic aromatic hydrocarbon; dG, deoxyguanosine; i.p., intraperitoneal; S9, postmitochondrial supernatant; BPDE, benzo[a]pyrene-7,8-dihydrodiol-9,1O-epoxide; DMSO, dimethyl sulfoxide; 9-OH-BP, 9-hydroxy-benzo[a]pyrene; PEI, pol yethyleneimine; TLC, thin-layer chromatography. 0 1993 Wiley-Liss, Inc. 152 Garg et al.