Hepatic metabolism of 7,12-dimethylbenz(a)anthracene in male, female, and ovariectomized Sprague-Dawley rats

Journal Article · Tue Jan 15 04:00:00 EST 1991 · Cancer Research; (USA)

OSTI ID:6143158

Vater, S T; Baldwin, D M; Warshawsky, D ^[1]

---

1. Univ. of Cincinnati Medical Center, OH (USA)

Dimethylbenz(a)anthracene (DMBA) is a potent inducer of mammary tumors in intact female Sprague-Dawley rats, but not in males or ovariectomized females (OVX). Qualitative and quantitative aspects of hepatic metabolism of DMBA were examined in these three groups of rats, using the nonrecirculating perfused liver, to determine whether the production of proximate carcinogenic metabolites of DMBA by the liver differed among these groups in the same manner as does sensitivity to tumor induction. DMBA was infused into the liver at a constant rate for 60 min. Rates of appearance of DMBA and its metabolites were measured in perfusate and bile during the infusion period and the first 60 min thereafter. The maximum rate of appearance of total metabolites in the perfusate, seen at the end of the infusion period, was highest in the intact female (2.6 +/- 0.3 nmol/(g x min)), slightly lower in the OVX (2.3 +/- 0.2 nmol/(g x min)) and significantly lower in the male (1.0 +/- 0.1 nmol/(g x min)). The rates of appearance of metabolites in the bile showed the same order as those seen in the perfusate. The major metabolites extracted from the perfusate in all three groups were dihydrodiols, hydroxymethyl metabolites, and several unidentified metabolites. The 3,4-dihydrodiol, a proximate carcinogenic metabolite, appeared in the perfusate at higher rates in the intact female and OVX than in the male. Hydrolysis of bile samples showed that glucuronidation was a major pathway in the excretion of DMBA metabolites in bile. High performance liquid chromatographic analysis indicated that hydrolysis of DMBA glucuronides yielded the 7- and 12-hydroxymethyl metabolites and an unidentified metabolite designated X. The major hydrolysis product in the male was 12-hydroxymethyl while X was found to be the major product in the intact female and OVX.

• OSTI ID: 6143158
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 51:2; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BENZANTHRACENE
BODY
CARCINOGENESIS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
EXPERIMENTAL NEOPLASMS
GLANDS
HYDROCARBONS
LIVER
MAMMALS
MAMMARY GLANDS
METABOLISM
METABOLITES
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PERFUSED ORGANS
RATS
RODENTS
SEX DEPENDENCE
VERTEBRATES