Mutagenicity of benzo(a)pyrenyl‐1‐sulfate in the Ames test

  title={Mutagenicity of benzo(a)pyrenyl‐1‐sulfate in the Ames test},
  author={S. E. Irwin and G. Kwei and G. Blackburn and R. Thurman and F. Kauffman},
  journal={Environmental and Molecular Mutagenesis},
Comparison of the mutagenicity of nine isomeric benzo(a)pyrenyl [B(a)P] phenols conjugated with either sulfate or glucuronide was carried out using strain Salmonella typhimurium TA98. Of the nine conjugates tested, only B(a)P‐1‐sulfate was mutagenic. Accordingly, the mutagenicity of B(a)P‐1‐sulfate was compared with that of B(a)P and 1‐hydroxybenzo(a)pyrene [B(a)P‐1‐OH] in the presence and absence of rat lung S9 and Aroclor‐induced liver S9 with and with out an NADPH‐generating system. B(a)P‐1… Expand
9 Citations
Predominance of glucuronidation over sulfation in metabolism of 1-hydroxybenzo[a]pyrene by isolated rat hepatocytes.
The rate of 1-hydroxybenzo[a]pyrene glucuronide production by intact cells corresponded well with the total activity of UDP-glucuronosyltransferase(s) determined in permeabilized hepatocytes. Expand
Biotransformation of the cyclopenta-fused polycyclic aromatic hydrocarbon benz[j]aceanthrylene in isolated rat liver cell: identification of nine new metabolites.
The metabolites identified support the notion that epoxidation at the cyclopenta region is an important activation step of B[j]A and sulfation appears to play a very important role in the conversion of hydroxylated B[J]A metabolites into more polar excretable products. Expand
Sulfonation in Chemical Carcinogenesis
“Sulfonation” is the term we use — in place of the commonly used, but less precise, term “sulfation” — for the sulfotransferase-catalyzed transfer of the sulfo group ( -SO3H , -SO 3 - ; Benkovic andExpand
Biologically Active Conjugates of Drugs and Toxic Chemicals
Conjugation reactions associated with metabolism of drugs and xenobiotics function primarily as detoxification pathways (Caldwell 1982); however, they also serve to convert drug metabolites either toExpand
Identification of pre- and pro-haptens with a β-galactosidase-expressing E. coli culture system for skin sensitization.
The results suggested that the present bacterial system incorporated with the microsomal activation system could be considered as a useful alternative method to classify not only direct-acting sensitizers but also pre- or pro-haptens requiring metabolic activation in vitro. Expand
The influence of chemical structure on the extent and sites of carcinogenesis for 522 rodent carcinogens and 55 different human carcinogen exposures.
It is concluded that putative genotoxic rodent carcinogenesis can be correlated both with chemical structure and the extent and nature of the induced effect, and that it is of clear relevance to humans. Expand
Tissue-Specific Metabolism of Benzene in Zymbal Gland and Other Solid Tumor Target Tissues in Rats
In vitro studies were carried out to investigate whether target organ susceptibility to benzene-induced solid tumor formation is governed by tissue-specific differences in metabolism. The ability ofExpand
Conjugation—Deconjugation Reactions in Drug Metabolism and Toxicity
  • F. Kauffman
  • Chemistry, Medicine
  • Handbook of Experimental Pharmacology
  • 1994
Advances in molecular biology describing important enzyme systems involved in drug conjugation and deconjugation reactions and recent work indicating the importance of drug and xenobiotic conjugatesExpand
Challenges and Directions for Future Research
Molecular biological approaches being used to define the genetic regulation and tissue distribution of hydrolases involved in processing chemical conjugates are reviewed in several chapters of this volume, since their role in regulating net conjugate production in intact cells is beginning to be recognized. Expand


Mutagenicity of benzo[a]pyrene bay-region sulfonates.
The extensive conversion of anti-BPDE to B[a]PT-10-sulfonate under conditions where sulfite enhances diolepoxide mutagenicity, supports this novel B,[a]P derivative as a mediator of the sulfite-dependent enhancement of B[ a]P genotoxicity. Expand
Characterization of mutagenic glucuronide formation from benzo(a)pyrene in the nonrecirculating perfused rat liver.
It is concluded that mutagens exported in bile from livers perfused with benzo(a)pyrene can be accounted for predominantly by hydrolysis products of phenolic glucuronides. Expand
Possible role of 6‐hydroxymethylbenzo[a]pyrene as a proximate carcinogen of benzo[a]pyrene and 6‐methylbenzo[a]pyrene
Observations are in accord with the hypothesis that methylation or hydroxymethylation is one of the first steps in metabolic activation of carcinogenic polycyclic hydrocarbons. Expand
Benzo[a]pyrene bay-region sulfonates, a novel class of reactive intermediates.
Support for a key role of BPT-10 sulfonate in the enhancement of anti-BPDE mutagenicity is provided by the findings on the reactivity of this compounds. Expand
Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection.
It is proposed that a ring system sufficiently planar for a stacking interaction with DNA base pairs and a part of the molecule capable of being metabolized to a reactive group are discussed in terms of the theory of frameshift mutagenesis. Expand
Metabolic activation of the carcinogen 6-hydroxymethylbenzo[a]pyrene: formation of an electrophilic sulfuric acid ester and benzylic DNA adducts in rat liver in vivo and in reactions in vitro.
The data indicate that the sulfotransferase activity in the rat liver for HMBP plays a major role in the benzylic DNA adduct formation from this hydrocarbon in rat liver in vivo. Expand
beta-Glucuronidase catalyzed hydrolysis of benzo(a)pyrene-3-glucuronide and binding to DNA.
Results suggest that conjugates of benzo(a)pyrene may be converted by beta-glucuronidase at intracellular and organ sites distal to the initial sites of oxygenation and conjugation of benzos(a]pyrene to activated intermediates that are possibly carcinogenic. Expand
The liver plays a central role in the mechanism of chemical carcinogenesis due to polycyclic aromatic hydrocarbons.
Data provide compelling evidence that the liver is the predominant site of conversion of B[a]P into polar metabolites which are transported to target tissues and subsequently bind to DNA. Expand
Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals.
There is a high correlation between carcinogenicity and mutagenicity: 90% (156/174) of carcinogens are mutagenic in the test and despite the severe limitations inherent in defining non-carcinogenicity, few "non-Carcinogens" show any degree of mutageniability. Expand
High-pressure liquid chromatographic separation of 10 benzo(a)pyrene phenols and the identification of 1-phenol and 7-phenol as new metabolites.
The separation of ten isomeric benzo(a)pyrene phenols has been accomplished by the use of high-pressure liquid chromatography utilizing a newly developed recycling technique and new column andExpand