Short-term effects of the tumor promoting polychlorinated biphenyl mixture, Aroclor 1254, on I-compounds in liver, kidney and lung DNA of male Sprague-Dawley rats

Characterization and Quantitative Analysis of DNA Adducts Formed from Lower Chlorinated PCB-Derived Quinones

“…In summary, we have demonstrated that PCB-derived para-quinones can bind to DNA in vitro to form adducts by Michael addition. One previous study found no detectable liver DNA adducts after treatment of Sprague-Dawley rats with Aroclor 1254 (28). This negative finding plus the fact that PCB mixtures and individual congeners have often been found negative in short-term tests for mutagenicity supported the notion that metabolic activation does not play a major role in PCB-induced toxicity or genotoxicity (2).…”

Characterization and Quantitative Analysis of DNA Adducts Formed from Lower Chlorinated PCB-Derived Quinones

“…In summary, we have demonstrated that PCB-derived para-quinones can bind to DNA in vitro to form adducts by Michael addition. One previous study found no detectable liver DNA adducts after treatment of Sprague-Dawley rats with Aroclor 1254 (28). This negative finding plus the fact that PCB mixtures and individual congeners have often been found negative in short-term tests for mutagenicity supported the notion that metabolic activation does not play a major role in PCB-induced toxicity or genotoxicity (2).…”

Induction of DNA adducts by several polychlorinated biphenyls

“…However, in vivo, no evidence for DNA reactivity could be observed, which might be the result of the low metabolic rate of these compounds using either higher-chlorinated [Nath et al, 1991;Whysner et al, 1998] or lower-chlorinated (this study) PCB mixtures. We therefore conclude that, although PCBs are capable of inducing genotoxic damage in unprotected DNA, cellular defense mechanisms are apparently capable of preventing DNA adduct formation after a single exposure in intact organisms.…”

“…Even in tissues with high PHS activity (e.g., prostate), which can be expected to result in increased formation of DNA-reactive metabolites, no DNA adducts were observed. The effects of Aroclor 1254 in vivo on DNA binding in liver, kidney, and lung in male Sprague-Dawley rats have been reported to imply a decrease in liver I-compounds, which are indigenous DNA adducts, whereas no reductions in DNA adduct levels were observed in lung and kidney DNA [Nath et al, 1991]. Moreover, Aroclor 1260 was tested for DNA adduct formation in the liver of B6C3F1 mice after either single-or 2-week dietary exposure.…”

Polychlorinated Biphenyls–Modulated Tumorigenesis in Sprague–Dawley Rats: Correlation with Mixed Function Oxidase Activities and Superoxide (O2•−) Formation Potentials and Implied Mode of Action

“…With respect to DNA binding, a presumed indicator of tumor initiation, some investigators have reported the formation of DNA adducts with quinones derived from individual nonpersistent PCB congeners in vitro (Arif et al, 2003;Srinivasan et al, 2001); protein, though not DNA, adducts with such quinones in short-term tests in vivo also using individual PCB congeners (Lin et al, 2000;Pereg et al, 2001); and hepatic mutations in rats treated with a monochlorobiphenyl (Lehmann et al, 2006). However, there is no evidence of PCB-DNA interaction products in Aroclor-dosed animals (Nath et al, 1991;Schilderman et al, 2000;Whysner et al, 1998). The results of all studies conducted to date on Aroclors and individual PCB congeners, however, are consistent with hepatotumorigenesis (HT) promotional activity, for both lowortho (''dioxin-like'') and multi-ortho (''phenobarbital [PB]like'') PCB congeners in two-stage bioassays (ATSDR, 2000;Buchmann et al, 1991;Glauert et al, 2001, Shirai, 1997.…”

Characterization and Quantitative Analysis of DNA Adducts Formed from Lower Chlorinated PCB-Derived Quinones

“…In summary, we have demonstrated that PCB-derived para-quinones can bind to DNA in vitro to form adducts by Michael addition. One previous study found no detectable liver DNA adducts after treatment of Sprague-Dawley rats with Aroclor 1254 (28). This negative finding plus the fact that PCB mixtures and individual congeners have often been found negative in short-term tests for mutagenicity supported the notion that metabolic activation does not play a major role in PCB-induced toxicity or genotoxicity (2).…”

Induction of DNA adducts by several polychlorinated biphenyls

“…However, in vivo, no evidence for DNA reactivity could be observed, which might be the result of the low metabolic rate of these compounds using either higher-chlorinated [Nath et al, 1991;Whysner et al, 1998] or lower-chlorinated (this study) PCB mixtures. We therefore conclude that, although PCBs are capable of inducing genotoxic damage in unprotected DNA, cellular defense mechanisms are apparently capable of preventing DNA adduct formation after a single exposure in intact organisms.…”

“…Even in tissues with high PHS activity (e.g., prostate), which can be expected to result in increased formation of DNA-reactive metabolites, no DNA adducts were observed. The effects of Aroclor 1254 in vivo on DNA binding in liver, kidney, and lung in male Sprague-Dawley rats have been reported to imply a decrease in liver I-compounds, which are indigenous DNA adducts, whereas no reductions in DNA adduct levels were observed in lung and kidney DNA [Nath et al, 1991]. Moreover, Aroclor 1260 was tested for DNA adduct formation in the liver of B6C3F1 mice after either single-or 2-week dietary exposure.…”

Polychlorinated Biphenyls–Modulated Tumorigenesis in Sprague–Dawley Rats: Correlation with Mixed Function Oxidase Activities and Superoxide (O2•−) Formation Potentials and Implied Mode of Action

“…With respect to DNA binding, a presumed indicator of tumor initiation, some investigators have reported the formation of DNA adducts with quinones derived from individual nonpersistent PCB congeners in vitro (Arif et al, 2003;Srinivasan et al, 2001); protein, though not DNA, adducts with such quinones in short-term tests in vivo also using individual PCB congeners (Lin et al, 2000;Pereg et al, 2001); and hepatic mutations in rats treated with a monochlorobiphenyl (Lehmann et al, 2006). However, there is no evidence of PCB-DNA interaction products in Aroclor-dosed animals (Nath et al, 1991;Schilderman et al, 2000;Whysner et al, 1998). The results of all studies conducted to date on Aroclors and individual PCB congeners, however, are consistent with hepatotumorigenesis (HT) promotional activity, for both lowortho (''dioxin-like'') and multi-ortho (''phenobarbital [PB]like'') PCB congeners in two-stage bioassays (ATSDR, 2000;Buchmann et al, 1991;Glauert et al, 2001, Shirai, 1997.…”

Characterization and Quantitative Analysis of DNA Adducts Formed from Lower Chlorinated PCB-Derived Quinones

“…In summary, we have demonstrated that PCB-derived para-quinones can bind to DNA in vitro to form adducts by Michael addition. One previous study found no detectable liver DNA adducts after treatment of Sprague-Dawley rats with Aroclor 1254 (28). This negative finding plus the fact that PCB mixtures and individual congeners have often been found negative in short-term tests for mutagenicity supported the notion that metabolic activation does not play a major role in PCB-induced toxicity or genotoxicity (2).…”

Induction of DNA adducts by several polychlorinated biphenyls

“…However, in vivo, no evidence for DNA reactivity could be observed, which might be the result of the low metabolic rate of these compounds using either higher-chlorinated [Nath et al, 1991;Whysner et al, 1998] or lower-chlorinated (this study) PCB mixtures. We therefore conclude that, although PCBs are capable of inducing genotoxic damage in unprotected DNA, cellular defense mechanisms are apparently capable of preventing DNA adduct formation after a single exposure in intact organisms.…”

“…Even in tissues with high PHS activity (e.g., prostate), which can be expected to result in increased formation of DNA-reactive metabolites, no DNA adducts were observed. The effects of Aroclor 1254 in vivo on DNA binding in liver, kidney, and lung in male Sprague-Dawley rats have been reported to imply a decrease in liver I-compounds, which are indigenous DNA adducts, whereas no reductions in DNA adduct levels were observed in lung and kidney DNA [Nath et al, 1991]. Moreover, Aroclor 1260 was tested for DNA adduct formation in the liver of B6C3F1 mice after either single-or 2-week dietary exposure.…”

Polychlorinated Biphenyls–Modulated Tumorigenesis in Sprague–Dawley Rats: Correlation with Mixed Function Oxidase Activities and Superoxide (O2•−) Formation Potentials and Implied Mode of Action

“…With respect to DNA binding, a presumed indicator of tumor initiation, some investigators have reported the formation of DNA adducts with quinones derived from individual nonpersistent PCB congeners in vitro (Arif et al, 2003;Srinivasan et al, 2001); protein, though not DNA, adducts with such quinones in short-term tests in vivo also using individual PCB congeners (Lin et al, 2000;Pereg et al, 2001); and hepatic mutations in rats treated with a monochlorobiphenyl (Lehmann et al, 2006). However, there is no evidence of PCB-DNA interaction products in Aroclor-dosed animals (Nath et al, 1991;Schilderman et al, 2000;Whysner et al, 1998). The results of all studies conducted to date on Aroclors and individual PCB congeners, however, are consistent with hepatotumorigenesis (HT) promotional activity, for both lowortho (''dioxin-like'') and multi-ortho (''phenobarbital [PB]like'') PCB congeners in two-stage bioassays (ATSDR, 2000;Buchmann et al, 1991;Glauert et al, 2001, Shirai, 1997.…”