Covalent binding of 1, 1, 1, 2-tetrachloroethane to nucleic acids as evidence of genotoxic activity

Annamaria Colacci, Silvana Bartoli, Bruna Bonora, Carlo Buttazzi, Giovanna Lattanzi, Mario Mazzullo, Alessandra Niero, Maria Paola Turina, Sandro Grilli

Research output: Contribution to journalArticle

Abstract

Twenty-two hours after ip administration to male Wistar rats and BALB/c mice, 1, 1, 1, 2 tetrachloroethane (1, 1, 1, 2-TTCE) is bound covalently to DNA, RNA, and proteins of liver, lung, kidney, and stomach. The in vivo reactivity leads to binding values to DNA generally higher in mouse organs than in rat organs. The covalent binding index (CBI) values (82 in mouse liver DNA and 40 in rat liver DNA) classify 1, 1, 1, 2-TTCE as a weak to moderate initiator. Both microsomal and cytosolic enzymatic systems from rat and mouse organs are capable of bioactivating 1, 1, 1, 2-TTCE in vitro. Liver fractions are the most effective. When the activating systems are simultaneously present in the incuba tion mixture a synergistic effect is observed. Unlike the related chemical 1, 1, 2, 2 tetrachloroethane (1, 1, 2, 2-TTCE), which is bioactivated only through an oxidative route, 1, 1, 1, 2-TTCE metabolism is carried on by oxidative and reductive pathways, both dependent on cytochrome P-450. 1, 1, 1, 2-TTCE is also bioactivated by microsomal CSH-transferases from liver and lung. These data further confirm that correlations exist between structure and genotoxic activity of halocompounds.

Original languageEnglish
Pages (from-to)485-495
Number of pages11
JournalJournal of Toxicology and Environmental Health
Volume26
Issue number4
DOIs
Publication statusPublished - Apr 1 1989

Fingerprint

Nucleic acids
Liver
Nucleic Acids
Rats
DNA
Lung
Transferases
RNA
Metabolism
Cytochrome P-450 Enzyme System
Wistar Rats
Stomach
1,1,1,2-tetrachloroethane
Proteins
Kidney

ASJC Scopus subject areas

  • Toxicology
  • Pollution

Cite this

Covalent binding of 1, 1, 1, 2-tetrachloroethane to nucleic acids as evidence of genotoxic activity. / Colacci, Annamaria; Bartoli, Silvana; Bonora, Bruna; Buttazzi, Carlo; Lattanzi, Giovanna; Mazzullo, Mario; Niero, Alessandra; Turina, Maria Paola; Grilli, Sandro.

In: Journal of Toxicology and Environmental Health, Vol. 26, No. 4, 01.04.1989, p. 485-495.

Research output: Contribution to journalArticle

Colacci, A, Bartoli, S, Bonora, B, Buttazzi, C, Lattanzi, G, Mazzullo, M, Niero, A, Turina, MP & Grilli, S 1989, 'Covalent binding of 1, 1, 1, 2-tetrachloroethane to nucleic acids as evidence of genotoxic activity', Journal of Toxicology and Environmental Health, vol. 26, no. 4, pp. 485-495. https://doi.org/10.1080/15287398909531271
Colacci, Annamaria ; Bartoli, Silvana ; Bonora, Bruna ; Buttazzi, Carlo ; Lattanzi, Giovanna ; Mazzullo, Mario ; Niero, Alessandra ; Turina, Maria Paola ; Grilli, Sandro. / Covalent binding of 1, 1, 1, 2-tetrachloroethane to nucleic acids as evidence of genotoxic activity. In: Journal of Toxicology and Environmental Health. 1989 ; Vol. 26, No. 4. pp. 485-495.
@article{c03147c352274dbeabe5d399183a626f,
title = "Covalent binding of 1, 1, 1, 2-tetrachloroethane to nucleic acids as evidence of genotoxic activity",
abstract = "Twenty-two hours after ip administration to male Wistar rats and BALB/c mice, 1, 1, 1, 2 tetrachloroethane (1, 1, 1, 2-TTCE) is bound covalently to DNA, RNA, and proteins of liver, lung, kidney, and stomach. The in vivo reactivity leads to binding values to DNA generally higher in mouse organs than in rat organs. The covalent binding index (CBI) values (82 in mouse liver DNA and 40 in rat liver DNA) classify 1, 1, 1, 2-TTCE as a weak to moderate initiator. Both microsomal and cytosolic enzymatic systems from rat and mouse organs are capable of bioactivating 1, 1, 1, 2-TTCE in vitro. Liver fractions are the most effective. When the activating systems are simultaneously present in the incuba tion mixture a synergistic effect is observed. Unlike the related chemical 1, 1, 2, 2 tetrachloroethane (1, 1, 2, 2-TTCE), which is bioactivated only through an oxidative route, 1, 1, 1, 2-TTCE metabolism is carried on by oxidative and reductive pathways, both dependent on cytochrome P-450. 1, 1, 1, 2-TTCE is also bioactivated by microsomal CSH-transferases from liver and lung. These data further confirm that correlations exist between structure and genotoxic activity of halocompounds.",
author = "Annamaria Colacci and Silvana Bartoli and Bruna Bonora and Carlo Buttazzi and Giovanna Lattanzi and Mario Mazzullo and Alessandra Niero and Turina, {Maria Paola} and Sandro Grilli",
year = "1989",
month = "4",
day = "1",
doi = "10.1080/15287398909531271",
language = "English",
volume = "26",
pages = "485--495",
journal = "Journal of Toxicology and Environmental Health - Part A: Current Issues",
issn = "1528-7394",
publisher = "Taylor and Francis Ltd.",
number = "4",

}

TY - JOUR

T1 - Covalent binding of 1, 1, 1, 2-tetrachloroethane to nucleic acids as evidence of genotoxic activity

AU - Colacci, Annamaria

AU - Bartoli, Silvana

AU - Bonora, Bruna

AU - Buttazzi, Carlo

AU - Lattanzi, Giovanna

AU - Mazzullo, Mario

AU - Niero, Alessandra

AU - Turina, Maria Paola

AU - Grilli, Sandro

PY - 1989/4/1

Y1 - 1989/4/1

N2 - Twenty-two hours after ip administration to male Wistar rats and BALB/c mice, 1, 1, 1, 2 tetrachloroethane (1, 1, 1, 2-TTCE) is bound covalently to DNA, RNA, and proteins of liver, lung, kidney, and stomach. The in vivo reactivity leads to binding values to DNA generally higher in mouse organs than in rat organs. The covalent binding index (CBI) values (82 in mouse liver DNA and 40 in rat liver DNA) classify 1, 1, 1, 2-TTCE as a weak to moderate initiator. Both microsomal and cytosolic enzymatic systems from rat and mouse organs are capable of bioactivating 1, 1, 1, 2-TTCE in vitro. Liver fractions are the most effective. When the activating systems are simultaneously present in the incuba tion mixture a synergistic effect is observed. Unlike the related chemical 1, 1, 2, 2 tetrachloroethane (1, 1, 2, 2-TTCE), which is bioactivated only through an oxidative route, 1, 1, 1, 2-TTCE metabolism is carried on by oxidative and reductive pathways, both dependent on cytochrome P-450. 1, 1, 1, 2-TTCE is also bioactivated by microsomal CSH-transferases from liver and lung. These data further confirm that correlations exist between structure and genotoxic activity of halocompounds.

AB - Twenty-two hours after ip administration to male Wistar rats and BALB/c mice, 1, 1, 1, 2 tetrachloroethane (1, 1, 1, 2-TTCE) is bound covalently to DNA, RNA, and proteins of liver, lung, kidney, and stomach. The in vivo reactivity leads to binding values to DNA generally higher in mouse organs than in rat organs. The covalent binding index (CBI) values (82 in mouse liver DNA and 40 in rat liver DNA) classify 1, 1, 1, 2-TTCE as a weak to moderate initiator. Both microsomal and cytosolic enzymatic systems from rat and mouse organs are capable of bioactivating 1, 1, 1, 2-TTCE in vitro. Liver fractions are the most effective. When the activating systems are simultaneously present in the incuba tion mixture a synergistic effect is observed. Unlike the related chemical 1, 1, 2, 2 tetrachloroethane (1, 1, 2, 2-TTCE), which is bioactivated only through an oxidative route, 1, 1, 1, 2-TTCE metabolism is carried on by oxidative and reductive pathways, both dependent on cytochrome P-450. 1, 1, 1, 2-TTCE is also bioactivated by microsomal CSH-transferases from liver and lung. These data further confirm that correlations exist between structure and genotoxic activity of halocompounds.

UR - http://www.scopus.com/inward/record.url?scp=0024559637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024559637&partnerID=8YFLogxK

U2 - 10.1080/15287398909531271

DO - 10.1080/15287398909531271

M3 - Article

C2 - 2468781

AN - SCOPUS:0024559637

VL - 26

SP - 485

EP - 495

JO - Journal of Toxicology and Environmental Health - Part A: Current Issues

JF - Journal of Toxicology and Environmental Health - Part A: Current Issues

SN - 1528-7394

IS - 4

ER -