Carcinogenesis of 4-aminobiphenyl in BALB/cStCrlfC3Hf/Nctr mice

Schieferstein, G.; Littlefield, Neil A.; Gaylor, David W.; Sheldon, Winslow G.; Burger, Gary T.

doi:10.1016/0277-5379(85)90227-5

Cited by 40 publications

(33 citation statements)

References 13 publications

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“…Since the opposite metabolic relationship is seen in male mice (Figure 3), hormonal influences may contribute to the balance between activation and detoxification. There was significant bladder hyperplasia at 75 to 300 ppm (14), but in the absence of high levels of DNA adducts there was apparently insufficient stimulus for tumorigenesis.…”

Section: Aromatic Aminesmentioning

confidence: 95%

“…At the highest doses, 110 and 220 ppm, the liver tumor incidence did not reach 10% ( Figure 3A), whereas in the bladder, the tumor increase was not significant at doses up to 28 ppm but was essentially linear from 55 to 220 ppm, reaching 82%. Bladder tumorigenesis was only significant at doses for which the incidence of bladder hyperplasia was >85% (14), suggesting that cell proliferation is a prerequisite for tumorigenesis in these male mice. In both tissues, DNA adducts ( Figure 3B3) increased linearly with dose and correlated well with tumorigenesis (i.e., adduct levels were 2-to 3-fold higher in bladder where the tumor incidence was also high, compared to liver where the tumor incidence was low).…”

Section: Aromatic Aminesmentioning

confidence: 96%

“…The dose range for females was higher than that for males because of lower toxicity. The liver tumor incidence at 24 months (14) increased linearly with dose for the first 5 doses but was the same at 150 and 300 ppm ( Figure 4A). The DNA adduct levels at 28 days (11) increased linearly for the first 4 doses and less than linearly at 150 and 300 ppm ( Figure 4B).…”

Section: Aromatic Aminesmentioning

confidence: 97%

“…Liver and bladder tumor incidences at 24 months (14) and DNA adducts at 28 days are shown in Figure 3. At the highest doses, 110 and 220 ppm, the liver tumor incidence did not reach 10% ( Figure 3A), whereas in the bladder, the tumor increase was not significant at doses up to 28 ppm but was essentially linear from 55 to 220 ppm, reaching 82%.…”

Section: Aromatic Aminesmentioning

confidence: 99%

“…A factor confounding this interpretation is the considerable toxicity associated with the 300-ppm dose, with fewer than 50% of the mice surviving 2 years of treatment. The low adduct accumulation (<75 fmoles/pg DNA) (11) and low tumor incidence (<20%) (14) in female mouse bladder may reflect the reduced availability of compound for detoxification resulting from extensive activation and DNA adduct formation in the liver. Or they may result from the low metabolic capacity of BALB/c female kidney microsomes described above (15).…”

Section: Aromatic Aminesmentioning

confidence: 99%

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DNA adduct measurements and tumor incidence during chronic carcinogen exposure in rodents.

Poirier

Beland

1994

Environ Health Perspect

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In an attempt to elucidate the relationship between DNA adduct formation and tumorigenesis, DNA adducts were measured in the livers and bladders of mice during chronic exposure to several different doses of 2-acetylaminofluorene (2-AAF) and 4-aminobiphenyl (4-ABP). Continuous oral administration of these compounds for 4 weeks produced an increase in DNA adduct formation during the first 2 weeks, followed by a plateau, which presumably occurred because the rate of adduct removal offset the rate of adduct formation. The quantity of DNA adducts present at equilibrium correlated directly with the carcinogen concentration; therefore, when exposure was continued for 4 weeks, DNA adducts that reflected the plateau level at each dose could be expressed as a function of dose. Liver and bladder DNA adduct profiles thus obtained during administration of multiple doses of 2-AAF (to female mice) and 4-ABP (to male and female mice) were compared to profiles for tumor incidences obtained during lifetime exposures to the same doses. These experiments demonstrated similar profiles for DNA adduct formation and tumorigenesis in liver. In the bladder, DNA adducts were linear, but tumors only appeared at the higher doses in conjunction with cell proliferation. In addition to these aromatic amines, similar data are available for aflatoxin B1, diethylnitrosamine, and (methyinitrosamino)-1-(3-pyridyl)-1-butanone (also known as nicotine-derived nitrosoketone). Of the nine different biological situations (carcinogen/species/sex/organ) for which data are available, correlations between steadystate DNA adduct levels and tumorigenic response at the different doses were linear in five of the nine biological models. When the relationship between DNA adduct formation and tumor incidence was not linear, the profiles observed were considered to be the result of tissue-specific phenomena such as metabolic activation, cell proliferation, or cytotoxicity. -Environ Health Perspect 102(Suppl 6): 161-165 (1994)

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Section: Aromatic Aminesmentioning

confidence: 95%

Section: Aromatic Aminesmentioning

confidence: 96%

Section: Aromatic Aminesmentioning

confidence: 97%

Section: Aromatic Aminesmentioning

confidence: 99%

Section: Aromatic Aminesmentioning

confidence: 99%

See 3 more Smart Citations

DNA adduct measurements and tumor incidence during chronic carcinogen exposure in rodents.

Poirier

Beland

1994

Environ Health Perspect

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4‐Aminodiphenyl 92‐67‐1

2004

Sax's Dangerous Properties of Industrial Materials

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Strong impact of sulfotransferases on DNA adduct formation by 4‐aminobiphenyl in bladder and liver in mice

Chen

Paonessa

et al. 2018

Cancer Medicine

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Bladder cancer risk is 3‐4 times higher in men than women, but the reason is poorly understood. In mice, male bladder is also more susceptible than female bladder to 4‐aminobiphenyl (ABP), a major human bladder carcinogen; however, female liver is more susceptible than male liver to ABP. We investigated the role of sulfotransferase (Sult) in gender‐related bladder and liver susceptibility to ABP. Sulfation reactions of aromatic amine bladder carcinogens catalyzed by Sult may generate highly unstable and toxic metabolites. Therefore, liver Sult may decrease bladder exposure to carcinogens by promoting their toxic reactions in the liver. Notably, the expression of several liver Sults is suppressed by androgen in male mice. Here, we show that two Sults are critical for gender‐related bladder susceptibility to ABP in mice. We measured tissue level of N‐(deoxyguanosin‐8‐yl)‐4‐aminobiphenyl (dG‐C8‐ABP), a principal ABP‐DNA adduct, as readout of tissue susceptibility to ABP. We identified Sutl1a1 and to a lesser extent Sult1d1 as Sults that promote dG‐C8‐ABP formation in hepatic cells. In mice, gender gap in bladder susceptibility to ABP was narrowed by knocking out Sult1a1 and was almost totally eliminated by knocking out both Sutl1a1 and Sult1d1. This was accompanied by dramatic decrease in ABP genotoxicity in the liver (>97%). These results show the strong impact of the Sults on bladder and liver susceptibility to a human carcinogen. Because liver expression of both Sult1a1 and Sutl1d1 is suppressed by androgen in male mice, our results suggest that androgen renders bladder more exposed to ABP in male mice by suppressing Sult‐mediated ABP metabolism in liver, which increases bladder delivery of carcinogenic metabolites.

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Carcinogenesis of 4-aminobiphenyl in BALB/cStCrlfC3Hf/Nctr mice

Cited by 40 publications

References 13 publications

DNA adduct measurements and tumor incidence during chronic carcinogen exposure in rodents.

DNA adduct measurements and tumor incidence during chronic carcinogen exposure in rodents.

4‐Aminodiphenyl 92‐67‐1

Strong impact of sulfotransferases on DNA adduct formation by 4‐aminobiphenyl in bladder and liver in mice

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