Quantitative cancer assessment for vinyl chloride: indications of early-life sensitivity

Cogliano, Vincent; Hiatt, Gerald F.; Den, Arnold

doi:10.1016/0300-483x(96)03390-2

Cited by 9 publications

(5 citation statements)

References 4 publications

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“…Age-dependent differences in metabolism, leading to increased formation of DNA-reactive metabolites and increased DNA alkylation, combined with differences in cell proliferation rates, are thought to account for the increased susceptibility of young animals to vinyl chloride carcinogenesis. Researchers from the US EPA have suggested a risk assessment framework for vinyl chloride exposure in which exposures to children are given greater weight (i.e., risk) compared to exposures later in life (Cogliano, Hiatt, and Den 1996).…”

Section: Cancermentioning

confidence: 99%

Differences Between Children and Adults: Implications for Risk Assessment at California EPA

et al. 2002

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The California legislature enacted a law requiring the California Environmental Protection Agency (Cal/EPA) Office of Environmental Health Hazard Assessment (OEHHA) to evaluate whether our risk assessment methodologies are adequately protective of infants and children. In addition both OEHHA and the California Air Resources Board must examine whether the Ambient Air Quality Standards set for criteria air pollutants and the health values developed for air toxics are adequately protective of infants and children. We have initiated a program to look at potential differences in response to toxicants between children and adults. We are evaluating this issue from the perspective of exposure differences as well as toxicokinetic and toxicodynamic differences between children and adults. Data on specific chemicals are rather limited. As a result, we will be pooling information to determine whether there are generic differences between children and adults that may be applicable to risk assessment in general or to risk assessment of specific classes of compounds. This paper discusses the rationale for approaching the issue of determining whether our risk assessment methods are adequate for infants and children and includes a discussion of some of the available information on both qualitative and quantitative differences in response to toxicants between children and adults or immature and mature laboratory animals. We provide examples of differences between children and adults in absorption, metabolism, and excretion of toxicants as well as qualitative differences in toxic response.

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Section: Cancermentioning

confidence: 99%

Differences Between Children and Adults: Implications for Risk Assessment at California EPA

et al. 2002

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“…Drew et al also reported that rats, mice, and hamsters exposed to 50–200 ppm VC by inhalation (6 h/day, 5 days/week), regardless of duration of exposure, had a higher incidence of neoplasms when exposures are started early in life . It was also shown that rat fetuses and neonates have higher susceptibility to angiosarcomas and hepatocellular carcinomas. , …”

Section: Introductionmentioning

confidence: 96%

“…42 It was also shown that rat fetuses and neonates have higher susceptibility to angiosarcomas, and hepatocellular carcinomas. 44, 45 …”

Section: Introductionmentioning

confidence: 99%

“…39,40 Previously, VC has been shown to be more carcinogenic in young animals. [41][42][43][44] showed that 1 day old Sprague−Dawley rats exposed to 6000 or 12000 ppm VC (4 h/day, 5 day/week, 5 weeks) had about a 50% incidence of angiosarcoma, whereas 13 week old rats exhibited less than a 10% incidence. 41 Drew et al also reported that rats, mice, and hamsters exposed to 50−200 ppm VC by inhalation (6 h/day, 5 days/week), regardless of duration of exposure, had a higher incidence of neoplasms when exposures are started early in life.…”

Section: ■ Introductionmentioning

confidence: 99%

“…42 It was also shown that rat fetuses and neonates have higher susceptibility to angiosarcomas and hepatocellular carcinomas. 44,45 Animal studies also indicated that young animals are more susceptible than adults to the formation of DNA adducts by VC exposures. 46−48 It was previously reported that following VC exposure via inhalation (600 ppm, 4 h/day, 5 days), 7-OEG and εG concentrations in 10 day old rats were ∼4-fold higher than lactating rats.…”

Section: ■ Introductionmentioning

confidence: 99%

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A New LC-MS/MS Method for the Quantification of Endogenous and Vinyl Chloride-Induced 7-(2-Oxoethyl)Guanine in Sprague–Dawley Rats

Mutlu¹,

Jeong²,

Collins³

et al. 2012

Chem. Res. Toxicol.

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Vinyl chloride (VC) is an industrial chemical that is known to be carcinogenic to animals and humans. VC primarily induces hepatic angiosarcomas following high exposures (≥50 ppm). VC is also found in Superfund sites at ppb concentrations as a result of microbial metabolism of trichloroethylene and perchloroethylene. Here, we report a new sensitive LC-MS/MS method to analyze the major DNA adduct formed by VC, 7-(2-oxoethylguanine) (7-OEG). We used this method to analyze tissue DNA from both adult and weanling rats exposed to 1100 ppm [13C2]-VC for 5 days. After neutral thermal hydrolysis, 7-OEG was derivatized with O-t-butyl hydroxylamine to an oxime adduct, followed by LC-MS/MS analysis. The limit of detection was 1 fmol and the limit of quantitation was 1.5 fmol on the column. The use of stable isotope VC allowed us to demonstrate for the first time that endogenous 7-OEG was present in tissue DNA. We hypothesized that endogenous 7-OEG was formed from lipid peroxidation and demonstrated the formation of [13C2]-7-OEG from the reaction of calf thymus DNA with [13C18]-ethyl linoleate (EtLa) under peroxidizing conditions. The concentrations of endogenous 7-OEG in liver, lung, kidney, spleen, testis and brain DNA from adult and weanling rats typically ranged from 1.0-10.0 adducts per 106 guanine. The exogenous 7-OEG in liver DNA from adult rats exposed to 1100 ppm [13C2]-VC for 5 days was 104.0 ± 23.0 adducts per 106 guanine (n=4), while concentrations in other tissues ranged from 1.0-39.0 adducts per 106 guanine (n=4). Although endogenous concentrations of 7-OEG in tissues in weanling rats were similar to those of adult rats, exogenous [13C2]-7-OEG concentrations were higher in weanlings, averaging 300 adducts per 106 guanine in liver. Studies on the persistence of [13C2]-7-OEG in adult rats sacrificed 2, 4, and 8 wks post exposure to [13C2]-VC demonstrated a half-life of 7-OEG of 4 days in both liver and lung.

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Effects of glucose on cloning efficiency and mutagenesis of fetal rat cells

Donovan

Smith

Riggs

et al. 2002

Teratog Carcinog Mutagen

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In a previous study, treatment of rats with 10% glucose in the drinking water, as fetuses during gestation and for 1.5 months after delivery, significantly enhanced tumor incidence that resulted from N-methyl-N-nitrosourea (MNU, 20 mg/kg) given transplacentally on gestation day 21, with a 1.6-fold increase in overall tumor incidence. We investigated whether glucose would have an effect on MNU-induced mutation in fetal F-344 rat somatic cells as measured in an in vivo/in vitro assay. Rat fetuses were exposed transplacentally to MNU on gestation day 16 and to a 10% glucose solution from gestation day 7 to day 17. Cells were isolated on gestation day 17 for determination of cloning efficiency and for selection of 6-thioguanine (6-TG)-resistant HGPRT mutants. Cloning efficiency of the fetal cells exposed to MNU alone was 22.6+/-2.3% S.E., while that for cells from fetuses exposed to MNU+glucose was 27.5+/-1.6% S.E., which was a significant difference (P=0.018). This indicates an effect of glucose on cell proliferation and survival. MNU treatment significantly increased the mutation frequency of fetal cells from a spontaneous value of 0.4 x 10(-6) per viable cell to (8.8+/-1.8 S.E.,) x 10(-6) (P=0.0087). The coexposure to MNU and glucose yielded a mutant frequency per plate of 0.62+/-0.05 S.E., which was a 1.5-fold increase compared to MNU alone (0.43+/-0.11 S.E., P=0.075. In summary, the data indicate that glucose during pregnancy increases proliferation/survival of fetal cells and possibly also mutation rate.

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Quantitative cancer assessment for vinyl chloride: indications of early-life sensitivity

Cited by 9 publications

References 4 publications

Differences Between Children and Adults: Implications for Risk Assessment at California EPA

Differences Between Children and Adults: Implications for Risk Assessment at California EPA

A New LC-MS/MS Method for the Quantification of Endogenous and Vinyl Chloride-Induced 7-(2-Oxoethyl)Guanine in Sprague–Dawley Rats

Effects of glucose on cloning efficiency and mutagenesis of fetal rat cells

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