Long-term inhalation study with benzo(a)pyrene and SO2 in Syrian golden hamsters

Pauluhn, Jürgen; Thyssen, J.; Althoff, J.; Kimmerle, Georg; Möhr, U.

doi:10.1016/s0232-1513(85)80029-3

Cited by 33 publications

(9 citation statements)

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“…Cell proliferation i s considered to be an important modulating factor in carcinogenesis, including carcinogenesis of the respiratory tract (Cohen and Ellwein, NO Witschi, 1991). Several studies have shown that an event that produces hyperplasia of the res iratory tract epithelia in hamsters may ical carcinogen (Little et al, 1978;Keenan et al, 1989aKeenan et al, , 1989bHeinrich et al, 1982;Pauluhn et al, 1985;Dalbey, 1982). Other studies with hamsters, however, fail to confirm such a conclusion (Feron et al, 1982;Hecht et al, 1983;Heinrich et al, 1986Heinrich et al, , 1989.…”

Section: Discussionmentioning

confidence: 99%

Modulation of N-Nitrosodiethylamine Induced Hamster Lung Tumors by Nitrogen Dioxide

Witschi

Breider

Schüller

1992

Inhalation Toxicology

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The objective o f the study was to examine whether continuous exposure to NO2 would modify the development o f chemically induced lung tumors. Male Syrian golden hamsters were treated, twice a week, with sc injections of Nnitrosodiethylamine (DEN) while being exposed for 23 h/d, 7 dlwk to 15 ppm o f NO,.Animals were sacrificed 4 mo and 6-8 m o after the beginning o f the experiment. No lung tumors were found in hamsters treated with DEN and exposed to NO2 whereas 26% o f the animals treated with DEN alone had peripheral lung tumors after 6-8 mo. The development of tracheal tumors was delayed b y exposure to the pollutant. The results o f the experiment do not allow implication o f NO2 as a possible enhancer o f respiratory tract tumors in hamsters.

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Section: Discussionmentioning

confidence: 99%

Modulation of N-Nitrosodiethylamine Induced Hamster Lung Tumors by Nitrogen Dioxide

Witschi

Breider

Schüller

1992

Inhalation Toxicology

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“…(Bi)sulfite exposure can produce an induction of an acute asthmatic state (3,20). (Bi)sulfite also appears to have genetic effects (21) and can act as a mutagen or comutagen (22) and a cocarcinogen (20,23). Laskin and coworkers (20) reported that sulfur dioxide was cocarcinogenic for development of benzo[a]pyreneinduced pulmonary carcinoma, which has been confirmed (23).…”

Section: Discussionmentioning

confidence: 99%

“…(Bi)sulfite also appears to have genetic effects (21) and can act as a mutagen or comutagen (22) and a cocarcinogen (20,23). Laskin and coworkers (20) reported that sulfur dioxide was cocarcinogenic for development of benzo[a]pyreneinduced pulmonary carcinoma, which has been confirmed (23). Our finding of (bi)sulfite-dependent generation of anti-BPDE, the ultimate carcinogenic form of benzo[a]pyrene, must be considered in light of this observed cocarcinogenic relationship.…”

Section: Discussionmentioning

confidence: 99%

Epoxidation of (+/-)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene during (bi)sulfite autoxidation: activation of a procarcinogen by a cocarcinogen.

Reed¹,

Curtis²,

Mottley³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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The (bi)sulfite ion undergoes extensive autoxidation in neutral aqueous media with the formation of sulfur trioxide radical anion that is detected by ESR. The radical anion subsequently reacts with molecular oxygen to form a peroxyl radical. We find that when (±)-trans-7, 8-dihydroxy-7,8-dihydrobenzo[a]pyrene is included in this autoxidation system, BP-7,8-diol is converted to diolepoxides, ultimate carcinogenic derivatives of benzo [a]pyrene. This epoxidation occurs with a stereoselectivity consistent with either a peroxyl radical or a peracid as the epoxidizing agent. The epoxidation is dependent on the concentration of both (bi)sulfite and oxygen. In the presence of 10 IAM butylated hydroxyanisole, which abolishes (bi)sulflte autoxidation, no (bi)sulfite-dependent epoxidation occurs. These results are discussed in regard to the mechanism of (bi)sulfite autoxidation, and in relationship to the cocarcinogenicity of sulfur dioxide [anhydrous (bi)sulfite] for benzo [a]pyrene-induced pulmonary neoplasia.Sulfur dioxide, an environmental pollutant, exists primarily as the (bi)sulfite anion in aqueous solution at near neutral pH. The metal-catalyzed autoxidation of the (bi)sulfite anion, studied for decades, is an oxygen-consuming chain reaction (1-3). The initiating one-electron oxidation yields the sulfur trioxide radical anion ('SO-), a predominantly sulfur-centered radical (4) that reacts with molecular oxygen. Superoxide initiates (bi)sulfite oxidation by forming 'SO (1, 5) but is not a chain propagator (2, 5), implying superoxide is not formed by reactions of the '0j radical. Presumably the reaction product of SO with oxygen is a peroxyl free radical.S53 + 02 -03SOO. [1] Huie and Neta (6) presented a kinetic argument favoring this oxygen addition reaction. Since this pathway produces a peroxyl free radical, we sought to obtain chemical support for the formation of -03SOO during (bi)sulfite autoxidation based on products of a specific trapping reaction.The trapping agent employed was (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene . This compound is stereoselectively epoxidized to form (+)-7r,8t-dihydroxy-9t, 10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) by either peroxyl radicals (7-10) or peracids (11)(12)(13). The inclusion of BP-7,8-diol in an aqueous system for (bi)sulfite autoxidation did indeed lead to the production of anti-BPDE. In this paper we present a characterization of this epoxidation and consider the implications ofthis reaction in regard to the mechanism of (bi)sulfite autoxidation and the Butylated hydroxyanisole (BHA), 5,5-dimethyl-1-pyrroline N-oxide (DMPO), superoxide dismutase, and diethylenetriaminepentaacetic acid (DETAPAC) were from Sigma. Potassium peroxomonosulfate (OXONE, DuPont) was obtained from Aldrich. Polyoxyethylene sorbitan monolaurate (Tween 20) and all chromatography solvents were from Fisher.Reaction Conditions. Tritiated and unlabeled BP-7,8-diol, in ethanol, were added to the reaction vessel, and the solvent was evaporated under a stream of N2. The r...

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“…These include oxidation of methionine (36), diphosphopyridine nucleotides (37), and lipids (38); destruction of n-carotene (8) and tryptophan (36); addition to double bonds in unsaturated fatty acids (39); and modification of nucleic acids (7,40). Some of these effects are potentially genotoxic and may contribute to carcinogenesis (3)(4)(5). The genotoxicity of -OH radical, also generated by sulfite oxidation, is well recognized (41).…”

Section: Methodsmentioning

confidence: 99%

“…Sulfite appears to have genotoxic effects (3). It can act as a mutagen or co-mutagen (4) and a co-carcinogen (5). The mechanism of sulfite toxicity is believed to be related to sulfite oxidation processes involving sulfur trioxide radical ion (-SO;) formation (1,(6)(7)(8) (-OH) radical is also generated in the sulfite oxidation pathway (9).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Generation of Hydroxyl Radical and Sulfur Trioxide Anion Radical from Oxidation of Sodium Sulfite, Nickel(II) Sulfite, and Nickel Subsulfide in the Presence of Nickel(II) Complexes

Shi¹,

Dalal²,

Kasprzak³

1994

Environmental Health Perspectives

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Electron spin resonance (ESR) spin trapping was utilized to investigate the generation of free radicals from oxidation of sodium sulfite, nickel(ll) sulfite, and nickel subsulfide (Ni3S2) by ambient oxygen or H202 at pH 7.4. The spin trap used was 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Under ambient oxygen, a solution of sodium sulfite alone generated predominantly sulfur trioxide anion radical (-SO0) due to the autoxidation of sulfite.Addition of nickel(ll) chloride [NiOllW] enhanced the -SO; yield about 4-fold. Incubation of sulfite with Ni(ll) in the presence of chelators such asand penicillamine did not have any significant effect on that enhancement. In contrast, albumin, and especially glycylglycylhistidine (GlyGlyHis), augmented the enhancing effect of Ni(ll) by factors of 1.4 and 4, respectively. Computer simulation analysis of the spin-adduct spectrum and formate scavenging experiment showed that the mixture of sodium sulfite, Ni(ll), and GlyGlyHis generated both hydroxyl (-OH) radical and -SO; radical, in the ratio of approximately 1:2. The free-radical spin adduct intensity reached its saturation level in about 5 min. The yield of the radical adducts could be slightly reduced by deferoxamine and very strongly reduced by diethylenetriaminepentaacetic acid (DTPA). Aqueous suspensions of sparingly soluble nickel(ll) sulfite in the presence of air and GlyGlyHis generated surface-located *SO-and 'OH radicals. The same radicals were generated in Ni3S2 suspension in the presence of GlyGlyHis and H202, indicating sulfite production by oxidation of the sulfide moiety of this compound. In view of the present results, the exceptionally high carcinogenic potential of Ni3S2 appears to be due to the ability of both the nickel and sulfide constituents of the molecule to facilitate the generation of genotoxic radicals. -Environ Health Perspect 102 (Suppl 31:91-96 (1994)

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Long-term inhalation study with benzo(a)pyrene and SO2 in Syrian golden hamsters

Cited by 33 publications

References 1 publication

Modulation of N-Nitrosodiethylamine Induced Hamster Lung Tumors by Nitrogen Dioxide

Modulation of N-Nitrosodiethylamine Induced Hamster Lung Tumors by Nitrogen Dioxide

Epoxidation of (+/-)-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene during (bi)sulfite autoxidation: activation of a procarcinogen by a cocarcinogen.

Enhanced Generation of Hydroxyl Radical and Sulfur Trioxide Anion Radical from Oxidation of Sodium Sulfite, Nickel(II) Sulfite, and Nickel Subsulfide in the Presence of Nickel(II) Complexes

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