Mutagenic DNA base modifications are correlated with lesions in nonneoplastic hepatic tissue of the English sole carcinogenesis model.
Hydroxyl radical-induced mutagenic base modifications have been linked to neoplasia in a number of biological systems, including English sole from chemically contaminated urban environments. However, virtually no information exists on the relationship between the mutagenic base modifications and preneoplastic and other lesions found in tumor-free tissues prone to cancer. We studied six hepatic lesions in immature, neoplasm-free English sole exposed to an urban and reference environment and established correlations between the lesion incidence and concentrations of the mutagenic base modifications 8-hydroxyguanine and 8-hydroxyadenine. The lesions were putatively preneoplastic basophilic foci, hepatocellular karyomegaly, megalocytic hepatosis, hepatocellular vacuolar change, hyalin droplet formation, and apoptosis. With the exception of hepatocellular vacuolar change, significant positive correlations were found between the lesions and the mutagenic base modifications. The hydroxyl radical may be a common etiological factor in the formation of the base modifications and hepatic lesions.
Malins
D C
DC
Molecular Epidemiology Program, Pacific Northwest Research Foundation, Seattle, Washington 98122, USA.
Polissar
N L
NL
Garner
M M
MM
Gunselman
S J
SJ
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D015986:Confounding Factors, Epidemiologic; D005393:Fish Diseases / Q000378:metabolism* / Q000473:pathology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D016296:Mutagenesis; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*
C002992:8-hydroxyadenine; C024829:8-hydroxyguanine; D006147:Guanine; D000225:Adenine