In vitro lymphotoxicity and selective T cell immunotoxicity of high doses of acyclovir and its derivatives in mice.
The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7-isomer (7-ACV) and its two derivatives: N2-acetyl ACV (ac-ACV) and N2,O-diacetyl ACV (diac-ACV) were examined for their potential in vitro lymphotoxicity and in vivo immunotoxicity in mice. In vitro lymphotoxicity of ACV and its acetylated derivatives was low, whereas the 7-ACV isomer enhanced the in vitro cell proliferation in PHA-stimulated cultures. Addition of 2'-deoxyguanosine (dGuo) did not exhibit any inhibitory potential of ACV. However, reduction in the absolute number of CD3+, CD8+, and CD25+ cells, but not Ig+ cells, was noted at high concentrations of ACV and its derivatives, suggesting a selective T cell cytotoxicity. Similarly, the in vivo exposure revealed selective T cell immunotoxicity of ACV and its derivatives since the reduced number of Thy 1.2+ and CD8+ cells was not accompanied with any marked changes in the Ig+ population. The CD4+/CD8+ ratio was affected both in vitro and in vivo by high concentrations of ACV.
Poluektova
L
L
Département des Sciences Biologiques and Toxen, Université du Québec à Montréal, Canada.
Krzystyniak
K
K
Desjardins
R
R
Flipo
D
D
Fournier
M
M
D000212:Acyclovir / Q000031:analogs & derivatives / Q000633:toxicity*; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis; D000998:Antiviral Agents / Q000633:toxicity*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010835:Phytohemagglutinins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000954:Antigens, Surface; D000998:Antiviral Agents; D010835:Phytohemagglutinins; D000212:Acyclovir