title: Effect of low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on influenza A virus-induced mortality in mice.
abstract: Dioxins, including the most toxic congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), exert diverse biological effects in humans and animals. Host resistance, especially to virus infections, is considered one of the most sensitive targets of TCDD-toxicity, while a recent study showed that the vulnerability to TCDD of host resistance to viruses varied form experiment to experiment. Burleson et al. [Fundam. Appl. Toxicol. 29 (1996) 40] reported that a single oral dose as low as 10 ng TCDD/kg increased the mortality of mice infected with influenza A virus. If this value had been adopted as the basis for the tolerable daily intake (TDI) of dioxins, the TDI of 1-4 pg toxic equivalent (TEQ)/kg per day recommended by WHO would have to be lower. In the present study, we used the same experimental protocol described by Burleson et al. to determine whether low-dose TCDD consistently compromises the host resistance of mice infected with influenza A virus. To do so, we investigated the effect of TCDD in the dose range of 0-500 ng/kg on the mortality of virus-infected female B6C3F1 mice. We also investigated the sex- and strain-dependency of host resistance in male B6C3F1 mice and in female C57Bl/6, Balb/c, and DBA/2 mice by administering the same dose range of TCDD. The results showed that TCDD doses up to 500 ng/kg did not increase the mortality of virus-infected mice in any of the strains. Further studies on the mechanism underlying the toxicity of TCDD are needed to assess the risk of exposure to this compound in influenza A virus infection.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, Onogawa, Ibaraki 305-8506, Tsukuba, Japan. keikon@nies.go.jp
authors.forename: Keiko
authors.initials: K
authors.lastname: Nohara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Izumi
authors.forename: Shin ichi
authors.initials: Si
authors.lastname: Tamura
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nagata
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D009980:Influenza A virus; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009976:Orthomyxoviridae Infections / Q000401:mortality* / Q000821:virology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012727:Sex Characteristics; D013045:Species Specificity; D016019:Survival Analysis
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins