Effect of particulates on metabolism and mutagenicity of benzo\[a\]pyrene

Our plain-English summary of Effect of particulates on metabolism and mutagenicity of benzo[a]pyrene, by D.R. Bevan, W.E. Manger (Chemico-biological Interactions, 1985).

The study

• Authors: D.R. Bevan, W.E. Manger
• Journal: Chemico-biological Interactions
• Published: 1985;56(1):13-28
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mechanisms of co-carcinogenicity of particulates, such as iron oxide and asbestos, and benzo[a]pyrene (B[a]P) are not completely understood. Particulates dramatically alter rates of uptake of B[a]P into membranes, a factor which could account for co-carcinogenicity. However, B[a]P must be activated to reactive forms to be carcinogenic and mutagenic so alterations in metabolism of B[a]P by particulates also could result in co-carcinogenesis. To elucidate mechanisms of particulate-B[a]P co-carcinogenesis, we have correlated rates of uptake of B[a]P into microsomes with metabolism of B[a]P and with mutagenicity of B[a]P in the Ames test. In general, aryl hydrocarbon hydroxylase (AHH) activity paralleled rates of uptake of B[a]P, though some inhibition of AHH activity by particulates which was not attributable to availability of B[a]P was evident. This inhibition was studied further by assaying separately mixed function oxidase and epoxide hydrase activities in the presence of particulates. Both chrysotile and iron oxide inhibited O-deethylation of 7-ethoxyresorufin and hydration of B[a]P-4,5-oxide. To determine effects of this inhibition on activation of B[a]P to reactive forms, we studied profiles of metabolites of B[a]P and mutagenicity of B[a]P. The only alteration in profiles of B[a]P metabolites produced by particulates was that due to effects on rates of uptake. Similarly, mutagenicity of B[a]P was positively correlated with rates of uptake into microsomes. We conclude that the predominant effects of chrysotile and iron oxide are in altering rates of uptake of particle-adsorbed B[a]P. Changes in uptake rates then result in alterations of B[a]P metabolism and mutagenicity.

In plain English

This laboratory study examined particulate effects on uptake, metabolism and mutagenicity of benzo[a]pyrene (B[a]P). B[a]P was added to rat liver microsomes (from 3-methylcholanthrene-treated rats) in acetone solution, as microcrystals, adsorbed to Canadian chrysotile asbestos or iron oxide, or mixed with particles lacking adsorbed B[a]P. Uptake was as rapid from the chrysotile-adsorbed state as from acetone solution, intermediate from the iron oxide-adsorbed state, and slowest from microcrystals; aryl hydrocarbon hydroxylase activity generally paralleled uptake, though particulates slightly lowered it. Chrysotile and iron oxide (2 mg) each lowered O-deethylation of 7-ethoxyresorufin (control 8.3 ± 1.7 nmol/min/mg; 4.0 ± 0.4 and 4.0 ± 2.7) and hydration of B[a]P-4,5-oxide (control 3.9 ± 0.4; 1.8 ± 0.2 and 1.3 ± 0.7). In the Ames test (strain TA100), revertants per plate (average ± S.E., 6 determinations) were 212 ± 24 (acetone), 156 ± 27 (chrysotile-adsorbed), 103 ± 22 (iron oxide-adsorbed), 82 ± 28 (microcrystals), 53 ± 14 (chrysotile alone), 56 ± 8 (iron oxide alone) and 43 ± 3 (spontaneous); a footnote stated the iron oxide-alone value differed significantly from spontaneous. The authors concluded the particulates acted predominantly by altering uptake rates.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: in vitro laboratory experiments: uptake, metabolism and enzyme assays in rat liver microsomes plus Ames bacterial mutagenicity testing
• Who was studied: Liver microsomes prepared from male Sprague-Dawley rats (200-250 g) pretreated with 3-methylcholanthrene, and Salmonella strain TA100 cultures in the Ames test
• Exposure: Benzo[a]pyrene presented in four physical forms: acetone solution, aqueous microcrystals, adsorbed to Canadian chrysotile asbestos or to iron oxide, and acetone or microcrystalline B[a]P mixed with particles lacking adsorbed B[a]P; 2 mg of chrysotile or iron oxide used in the enzyme assays
• Main results:
  • Uptake of B[a]P into microsomes from the chrysotile-adsorbed state was as rapid as from acetone solution, while uptake from the iron oxide-adsorbed state was intermediate between acetone solution/chrysotile and microcrystals
  • Particulates added without adsorbed B[a]P did not change the rate of transfer of B[a]P to microsomes
  • AHH activity broadly followed uptake rates, but particulates appeared to diminish it slightly; with iron oxide-adsorbed B[a]P it was only slightly higher than with microcrystals
  • Enzyme assays with 2 mg particles: O-deethylation of 7-ethoxyresorufin was 8.3 ± 1.7 nmol/min/mg (control), 4.0 ± 0.4 (chrysotile) and 4.0 ± 2.7 (iron oxide); hydration of B[a]P-4,5-oxide was 3.9 ± 0.4 (control), 1.8 ± 0.2 (chrysotile) and 1.3 ± 0.7 (iron oxide), particle values reported as significantly different from control, P < 0.05
  • Metabolite profiles: the only change produced by particulates was attributed to effects on uptake rate
  • Ames test revertants per plate, average ± S.E. for 6 determinations: B[a]P in acetone 212 ± 24, B[a]P adsorbed to chrysotile 156 ± 27, B[a]P adsorbed to iron oxide 103 ± 22, B[a]P microcrystals 82 ± 28, chrysotile alone 53 ± 14, iron oxide alone 56 ± 8, spontaneous 43 ± 3
  • The text stated that chrysotile or iron oxide added alone gave revertant numbers similar to spontaneous revertants, but the footnote to the iron oxide-alone value stated it was significantly different from B[a]P microcrystals + iron oxide and from spontaneous, though not from chrysotile (P less than or equal to 0.05)
• The authors' conclusion: The authors concluded that the main effect of chrysotile and iron oxide was to change the rate of uptake of particle-adsorbed B[a]P into membranes, and that these uptake changes then altered B[a]P metabolism and mutagenicity
• Limitations the authors state:
  • Standard errors in the microcrystal metabolism experiments were very large and their origin was not known with certainty
  • Effects of particles lacking adsorbed B[a]P on AHH activity with microcrystalline B[a]P could not be discerned because activity was very low
  • The authors noted that mechanisms other than particle-enhanced uptake may contribute to co-carcinogenesis, particularly in human exposures
  • Reasons why inhibition of the metabolizing enzymes did not change metabolite profiles were not obvious to the authors

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Carcinogenic, Carcinogenesis, Chrysotile.

Related studies

• Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test — K. Szyba, A. Lange (1983)
• Effects of asbetos, iron oxide, silica, and carbon black on the microsomal availability of benzo[a]pyrene — J.R. Lakowicz, D.R. Bevan (1979)
• Effect of chrysotile asbestos and silica on the microsomal metabolism of benzo(a)pyrene — C. Kandaswami, P.J. O'Brien (1983)
• Effects of asbestos on membrane transport and metabolism of benzo(a)pyrene — C. Kandaswami, P.J. O'Brien (1980)
• Benzo[a]pyrene uptake into rat liver microsomes: effects of adsorption of benzo[a]pyrene to asbestos and non-fibrous mineral particulates — J.R. Lakowicz, D.R. Bevan (1980)
• On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: I. Urinary and serum mutagenicity studies with rats — C. Varga, G. Horváth, et al. (1998)

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