Chemically induced immunotoxicity in a medium-term multiorgan bioassay for carcinogenesis with Wistar rats.
A variety of chemicals can adversely affect the immune system and influence tumor development. The modifying potential of chemical carcinogens on the lymphoid organs and cytokine production of rats submitted to a medium-term initiation-promotion bioassay for carcinogenesis was investigated. Male Wistar rats were sequentially initiated with N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4hydroxybutyl)nitrosamine (BBN), dihydroxy-di-n-propylnitrosamine (DHPN), and 1,2-dimethylhydrazine (DMH) during 4 weeks. Two initiated groups received phenobarbital (PB) or 2-acetylaminofluorene (2-AAF) for 25 weeks and two noninitiated groups received only PB or 2-AAF. A nontreated group was used as control. Lymphohematopoietic organs, liver, kidneys, lung, intestines, and Zymbal's gland were removed for histological analysis. Interleukin (IL)-2, IL-12, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), IL-10, and transforming growth factor beta1 (TGF-beta1) levels were determined by ELISA in spleen cell culture supernatants. At the fourth week, exposure to the initiating carcinogens resulted in cell depletion of the thymus, spleen and bone marrow, and impairment of IL-2, IL-12, and IFN-gamma production. However, at the 30th week, no important alterations were observed both in lymphoid organs and cytokine production in the different groups. The results indicate that the initiating carcinogens used in the present protocol exert toxic effects on the lymphoid organs and affect the production of cytokines at the initiation step of carcinogenesis. This early and reversible depression of the immune surveillance may contribute to the survival of initiated cells facilitating the development of future neoplasia.
Spinardi-Barbisan
Ana Lúcia Tozzi
AL
Departamento de Patologia, TOXICAN, Faculdade de Medicina, UNESP, 18618-000 Botucatu, SP, Brazil.
Kaneno
Ramon
R
Barbisan
Luís Fernando
LF
Viana de Camargo
João Lauro
JL
Rodrigues
Maria Aparecida Marchesan
MA
D000818:Animals; D001681:Biological Assay / Q000379:methods*; D001835:Body Weight / Q000187:drug effects; D019046:Bone Marrow Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013160:Splenic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D013953:Thymus Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
D002273:Carcinogens; D016207:Cytokines; D009153:Mutagens