Benzo\[a\]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats

Our plain-English summary of Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats, by J. Topinka, P. Loli, M. Hurbáková, et al (Mutation Research, 2006).

The study

• Authors: J. Topinka, P. Loli, M. Hurbáková, Z. Kováciková, K. Volkovová, T. Wolff, D. Oesterle, S.A. Kyrtopoulos, P. Georgiadis
• Journal: Mutation Research
• Published: 2006;595(1-2):167-73
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In an attempt to examine the interaction of man-made mineral fibres with benzo[a]pyrene (B[a]P), homozygous X-lacI transgenic F344 rats were intratracheally treated with rock (stone) wool RWI and glass wool MMVF 10 fibres together with B[a]P. To analyze the induction of gene mutations by fibres and B[a]P in lung, single doses of 1 and 2 mg fibres/animal or multiple doses of 2 mg fibres/animal were administered weekly on 4 consecutive weeks (total dose 8 mg/animal). B[a]P (10 mg/animal) was administered either simultaneously with fibres (for single dose treatment with fibres) or together with the last fiber treatment (for multiple dose treatment with fibres). Animals were scarified 4 weeks after the last treatment. Benzo[a]pyrene administered simultaneously with RW1 fibres exhibited a strong synergistic effect on mutagenicity, the observed mutant frequency (MF) being more than three-fold higher than the net sum of the MF induced after separate administration of both agents. Our data suggest that DNA adducts induced by simultaneous B[a]P and fiber treatment lead to a strong increase in mutatant frequencies.

In plain English

This animal experiment used Big Blue (lambda-lacI) transgenic rats, which carry a gene used to count mutations. The authors tested rock (stone) wool RW1 and glass wool MMVF 10, not asbestos. Fibres were put directly into the windpipe as a single 1 or 2 mg dose, or 2 mg weekly for 4 weeks, with or without 10 mg of benzo[a]pyrene (B[a]P), a tobacco-smoke carcinogen. Groups had 3 to 5 rats, and lungs were examined 4 weeks after the last treatment. B[a]P alone significantly raised the lung mutation frequency, and neither fibre alone did. B[a]P alone gave 61.3 mutants per million plaque forming units, and adding 1 mg of RW1 gave 126.8. With single 1 or 2 mg RW1 doses plus B[a]P, the net mutation frequency was more than three times the sum of the two agents' separate effects. MMVF 10 plus B[a]P was more than additive only at the highest fibre dose. Adduct (B[a]P DNA damage) levels with fibres did not differ significantly from B[a]P alone. An oxidative-damage marker did not differ significantly from controls. The authors urged caution given the model's limits.

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: Animal experiment: intratracheal instillation (placing material directly into the windpipe) in transgenic rats, with lung mutation analysis
• Who was studied: Big Blue (lambda-lacI) transgenic F344 rats in treatment groups of 3 to 5 animals. The animals were killed 4 weeks after the last treatment.
• Exposure: Rock (stone) wool RW1 and glass wool MMVF 10 fibres. Doses were a single 1 mg or 2 mg dose, or 2 mg weekly for 4 weeks (4 × 2 mg, 8 mg total). Fibres were given alone or with B[a]P (10 mg per animal), and control rats received saline only. Asbestos was not tested in this study. Amosite data from the authors' earlier study are shown only for comparison.
• Main results:
  • B[a]P alone significantly increased the lung mutant frequency (p = 0.006). Single or multiple treatments with RW1 fibres alone did not have a significant mutagenic effect.
  • B[a]P alone gave a mutant frequency of 61.3 plus or minus 19.9 mutants per 10^6 plaque forming units (PFU). B[a]P plus 1 mg of RW1 gave 126.8 plus or minus 5.6 mutants per 10^6 PFU (p less than 0.004). The 2 mg RW1 dose with B[a]P gave a slight further increase. The 4 × 2 mg RW1 dose with B[a]P gave no further increase.
  • For the single 1 mg and 2 mg RW1 doses given with B[a]P, the net induced mutant frequency was more than three times the additive effect of the fibres and B[a]P given separately.
  • MMVF 10 glass wool fibres alone were not mutagenic at any dose or duration. Combined with B[a]P, MMVF 10 produced a super-additive mutagenic effect only at the highest dose (4 × 2 mg). No synergy was seen with the single 1 mg or 2 mg doses.
  • B[a]P-specific DNA adduct levels in rats given fibres plus B[a]P did not differ significantly from those in rats given B[a]P alone.
  • Lung malondialdehyde, a marker of oxidative damage, showed no significant difference from the control group after combined exposure to any dose of either fibre with B[a]P.
• The authors' conclusion: The authors concluded that co-exposure to RW1 and B[a]P produced mutagenic effects after a 4-week observation period. They noted that RW1 alone had been mutagenic only after 16 weeks in their earlier study. They said this underlines the potential contribution of tobacco smoke components to the cancer risk of fibres. They also called for further inhalation studies to estimate cancer risk in humans.
• Limitations the authors state:
  • The authors said the results should be interpreted with caution, given the limitations of the model system.
  • The authors said the complexity of tobacco smoke and fibre effects meant they could not identify the exact mechanism. They noted that tobacco smoke components other than B[a]P, such as nitrosamines, could also matter.

Topics

Medical terms in this study, explained in our Lexicon: Synergistic Effect, DNA adducts.

Related studies

• Benzo[a]pyrene-enhanced mutagenesis by asbestos in the lung of lambda-lacI transgenic rats — P. Loli, J. Topinka, et al. (2004)
• Mutagenesis by asbestos in the lung of lambda-lacI transgenic rats — J. Topinka, P. Loli, et al. (2004)
• 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)
• P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats — K. Unfried, N. Kociok, et al. (1997)
• On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: II. Tissue specificity studies using comet assay — C. Varga, G. Horváth, et al. (1999)
• Morphological transformation of Syrian hamster embryo cells induced by mineral fibres and the alleged enhancement of benzo[a]pyrene — S.O. Mikalsen, E. Rivedal, et al. (1988)

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