Table 1.
Primary DNA damage induced by pyrrolizidine alkaloids
| Agent | Testing system | Result | Reference |
|---|---|---|---|
| DNA adducts Comfrey root extract/comfrey compound oil | In vivo 32P-postlabeling/HPLC analysis | DHP-derived DNA adducts were formed in rat liver | Chou and Fu (2006) |
| Clivorine | In vitro 32P-postlabeling/HPLC analysis with metabolic activation | DHP-derived DNA adducts were formed in vitro | Xia et al. (2004) |
| Coltsfoot root extract | In vivo 32P-postlabeling/HPLC analysis | DHP-derived DNA adducts were formed in rat liver | Chou and Fu (2006) |
| Flos farfara Extract | In vivo 32P-postlabeling/HPLC analysis | DHP-derived DNA adducts were formed in rat liver | Chou and Fu (2006) |
| Heliotrine | In vitro 32P-postlabeling/HPLC analysis with metabolic activation | DHP-derived DNA adducts were formed | Xia et al. (2008) |
| Ligularia hodgsonnii extracts | In vitro 32P-postlabeling/HPLC analysis with metabolic activation | DHP-derived DNA adducts were formed | Xia et al. (2004) |
| Lasiocarpine | In vitro 32P-postlabeling/HPLC analysis with metabolic activation | DHP-derived DNA adducts were formed | Xia et al. (2006) |
| Monocrotaline | In vivo or in vitro with metabolic activation 32P-postlabeling/HPLC analysis | DHP-derived DNA adducts were formed in vitro and in rat liver | Wang et al. (2005b) |
| Retrorsine | In vivo or in vitro with metabolic activation 32P-postlabeling/HPLC analysis | DHP-derived DNA adducts were formed in vitro and in rat liver | Wang et al. (2005a) |
| Riddelliine | In vivo or in vitro with metabolic activation 32P-postlabeling/HPLC analysis | Two enantiomers of DHP-7deoxyguanosin-2N-yl adducts and DHP-modified dinucleotides were formed in vitro and in rat liver | Chou et al. (2003a–c, 2004); Xia et al. (2003); Yang et al. (2001) |
| Senecionine | In vivo covalent binding analysis in rat using 3H labeling | Uncharacterized DNA adducts were identified in rat liver, lung and kidney | Candrian et al. (1985) |
| Seneciphylline | In vivo covalent binding analysis in rat using 3H labeling | Uncharacterized DNA adducts were identified in rat liver, lung and kidney | Candrian et al. (1985) |
| DNA cross-linking Heliosupine | In vitro cells | DNA–DNA crosslinks | Hincks et al. (1991) |
| Jacobine | Alkaline elution in rat liver | DNA–DNA crosslinks DNA–protein crosslinks |
Petry et al. (1986) |
| Latifoline | In vitro cells | DNA–DNA crosslinks | Hincks et al. (1991) |
| Monocrotaline (Dehydromonocrotaline) |
In vitro cross-linking assay of PA-exposed cells or pyrrolic PA-exposed nucleiIn vivo and in vitro alkaline elution assay |
DNA–DNA crosslinks DNA–protein crosslinks |
Coulombe et al. (1999); Kim et al. (1995); Pereira et al. (1998); Petry et al. (1984); Petry and Sipes (1987); Rieben and Coulombe (2004); Tepe and Williams (1999); Wagner et al. (1993); Weidner et al. (1990) |
| Retrorsine (dehydroretronecine) | In vitro cross-linking assay of PA-exposed cells or pyrrolic PA-exposed nuclei | DNA–DNA crosslinks | Hincks et al. (1991); Reed et al. (1988) |
| Riddelliine (dehydroriddelliine) |
In vitro cross-linking assay of PA-exposed cells or pyrrolic PA-exposed nuclei |
DNA–protein crosslinks DNA–DNA crosslinks |
Hincks et al. (1991); Kim et al. (1995, 1999) |
| Senecionine (dehydrosenecionine) |
In vitro cross-linking assay of PA-exposed cells or pyrrolic PA-exposed nuclei |
DNA–protein crosslinks DNA–DNA crosslinks |
Coulombe et al. (1999); Hincks et al. (1991); Kim et al. (1995, 1999) |
| Seneciphylline (dehydroseneciphylline) |
In vitro cross-linking assay of PA-exposed cells or pyrrolic PA-exposed nuclei |
DNA–protein crosslinks DNA–DNA crosslinks |
Hincks et al. (1991); Kim et al. (1995) |
| DNA strand break Heliosupine | In vitro alkaline elution | Negative | Hincks et al. (1991) |
| Isatidin | In vitro comet assay | Positive | Uhl et al. (2000) |
| Jacobine | In vivo alkaline elution | Negative | Petry et al. (1986) |
| Latifoline | In vitro alkaline elution | Negative | Hincks et al. (1991) |
| Monocrotaline | In vitro alkaline elution | Negative | Hincks et al. (1991); Petry et al. (1984) |
| Monocrotaline | In vitro comet assay | Positive | Silva-Neto et al. (2010) |
| Retrorsine | In vitro alkaline elution | Negative | Hincks et al. (1991) |
| Riddelliine | In vitro alkaline elution | Negative | Hincks et al. (1991) |
| senecionine | In vitro alkaline elution | Negative | Hincks et al. (1991) |
| seneciphylline | In vitro alkaline elution | Negative | Hincks et al. (1991) |
| Unscheduled DNA synthesis Retrorsine | In rat hepatocytes following in vivo treatment | Positive | Griffin and Segall (1986) |
| Riddelliine | In rat and mouse hepatocytes following in vivo treatment | Positive | Chan (1993); Chan et al. (1994); Mirsalis (1987); Mirsalis et al. (1993); NTP (2003) |
| Senecionine | In rat hepatocytes following in vivo treatment | Positive | Griffin and Segall (1986) |
| Seneciphylline | In rat hepatocytes following in vivo treatment | Positive | Griffin and Segall (1986) |
Note: the pyrrolic PAs in brackets were also measured.