EurekaMag.com logo
+ Site Statistics
References:
53,214,146
Abstracts:
29,074,682
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Formation in isolated rat liver microsomes and nuclei of benzo(a)pyrene metabolites that bind to DNA






Cancer Research 36(11 Pt 1): 4107-4113

Formation in isolated rat liver microsomes and nuclei of benzo(a)pyrene metabolites that bind to DNA

The hepatic nuclear fraction isolated from 3-methylcholanthrene (MC)-treated rats contained enhanced levels of cytochrome P-450 and aryl hydrocarbon hydroxylase [benzo(a)pyrene (BP) monooxygenase], whereas the activities of epoxide hydrase and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase and the concentration of cytochrome b5 were not altered. The metabolite pattern of BP was investigated by using high-pressure liquid chromatography and was found to be similar in nuclei and microsomes from MC-treated rats. After incubation of the nuclear fraction with [3H]BP and reduced nicotinamide adenine dinculeotide phosphate, radioactivity was found to be associated with nuclear DNA and the extent of binding was markedly enhanced by pretreatment of the animals with MC. Binding was strongly inhibited by a-napthoflavone but was not influenced by 1,1,1-trichloropropene-2,3-oxide, an inhibitor of epoxide hydrase. In the presence of microsomes from MC-treated rats, increased binding of BP to DNA was observed in nuclei from both control and MC-treated rats; moreover, when the nuclear DNA was replaced by a corresponding amount of calf thymus DNA, the extent of binding was severalfold enhanced. In contrast to nuclei from control rats, the nuclear fraction from MC-treated rats showed an increase in bound radioactivity when incubated with a microsome-free supernatant, obtained by incubating microsomes from MC-treated rats with [3H]BP. The increase in extent of binding was eliminated in the presence of menadione or alpha-naphthoflavone. It is suggested that under the conditions used here the following different processes may have contributed to the total incorporation of BP products into nuclear DNA: (a) formation of DNA-binding products derived from BP by nuclear aryl hydrocarbon hydroxylase; (b) formation of DNA-binding products from microsomal BP metabolites by nuclear aryl hydrocarbon hydroxylase; and (c) direct transfer of reactive microsomal metabolites to nuclear DNA.

(PDF 0-2 workdays service: $29.90)

Accession: 038940816

PMID: 10077



Related references

Formation of DNA-binding products from isolated benzo[a]pyrene metabolites in rat liver nuclei. Chemico-Biological Interactions 20(3): 311-321, 1978

Metabolism of benzo a pyrene and levo trans 7 8 di hydroxy 7 8 di hydro benzo a pyrene by rat liver nuclei and microsomes. Cancer Research 38(5): 1241-1245, 1978

Binding of benzo a pyrene metabolites to dna in isolated rat liver nuclei. Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie 357(8): 1032, 1976

The binding of the benzo a pyrene metabolites to the dna of isolated rat liver nuclei and nuclear matrix. Biochemical Pharmacology 34(3): 385-386, 1985

The benzo a pyrene deoxy ribo nucleoside products isolated from dna after metabolism of benzo a pyrene by rat liver microsomes in the presence of dna. Cancer Research 35(5): 1263-1269, 1975

Relationship between the rate of reduction of benzo(a)pyrene-3,6-quinone and the formation of benzo(a)pyrene-3,6-quinol glucuronides in rat liver microsomes. Biochemical Pharmacology 34(6): 895-897, 1985

Metabolism of benzo(a)pyrene and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene by rat liver nuclei and microsomes. Cancer Research 38(5): 1241-1245, 1978

Effects of inducers and inhibitors of the benzo(a)pyrene hydroxylase of isolated rat liver nuclei and nuclear envelopes on the binding of benzo(a)pyrene to DNA. European Journal of Cancer 13(8): 847-853, 1977

Metabolism of benzo a pyrene 3 6 quinone and 3 hydroxy benzo a pyrene in liver microsomes from 3 methyl cholanthrene treated rats a possible role of dt diaphorase ec 1.6.99.2 in the formation of glucuronyl conjugates. Archives of Biochemistry and Biophysics 190(1): 97-108, 1978

The benzo(alpha)pyrene deoxyribonucleoside products isolated from DNA after metabolism of benzo(alpha)pyrene by rat liver microsomes in the presence of DNA. Cancer Research 35(5): 1263-1269, 1975