Potency of carcinogens derived from covalent DNA binding and stimulation of DNA synthesis in rat liver.

Abstract:

:In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrachloride (all known to be genotoxic via DNA binding) did not affect cell division, whereas several hepatocarcinogens known not to bind to DNA (alpha-HCH, clofibrate, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) gave rise to a dose-dependent stimulation of liver DNA synthesis within 24 h. An equation combining the influences of mitotic stimulation, expressed as dose required to double the control level of DNA synthesis, and DNA binding potency, expressed as the Covalent Binding Index, correlated well with the carcinogenic potency for both classes of hepatocarcinogens.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Lutz WK,Büsser MT,Sagelsdorff P

doi

10.1177/019262338401200118

subject

Has Abstract

pub_date

1984-01-01 00:00:00

pages

106-11

issue

1

eissn

0192-6233

issn

1533-1601

journal_volume

12

pub_type

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