7H-Dibenzo(c,g)carbazole-DNA Adducts in Target and Non-target Organs of Mice Exposed by Acute and Chronic Administration

Abstract

Carcinogen-DNA adducts appear to be biomarkers of effective dose and/or early effect. The relationship between these biomarker levels in target and non-target organs under acute and chronic exposures is important. 7H-Dibenzo(c,g)carbazole(DBC) has been shown to induce tumors in experimental animals. The time courses of DBC-DNA adduct formation in skin, liver and lung following both single (i.p.) and repeated (topical) administration of DBC were investigated. In the acute study, DNA binding levels increased rapidly in the lung over 3–7 days at all doses and then decreased slowly over 21 days; levels in the liver were 10 times that in the lung with similar increases in levels over time. In the chronic study, levels increased with time over 15 weeks with the liver binding levels 8–10 times that seen in skin and lung. In both studies the major adduct in liver was adduct 6, and in the lung adduct 3, while in skin adducts 2 and 3 were the major adducts. These data indicate that the adduct pattern is target organ specific, irrespective of the route, dose of administration or exposure regimen.

Key Words:

• 7H-Dibenzo(c,g)carbazole
• carcinogen DNA adducts
• chronic and acute exposure
• target organs-skin
• liver and lung
• biomarkers