Targeting of chemical mutagens to differentiating B-lymphocytes in vivo: detection by direct DNA labeling and sister chromatid exchange induction
In vivo systems for analyzing mutagen interactions with a specific differentiating cell population are rare. Taking advantage of the unique anatomical features of the bursa of Fabricius in the chicken, the authors explored the possibility of targeting chemical mutagens to a defined differentiating cell population in the animal, namely, the B-lymphocytes series. Such cells are known to be the targets for the oncogene-activating avian leukosis virus. Targeting of chemicals to cells of the bursa was demonstrated by application of the DNA-specific fluorochrome 4'-6-diamidino-2-phenylindole (DAPI) to the anal lips of neonatal chicks. Bright nuclear fluorescence of cells in the bursa demonstrated to occur within minutes after the application of 500..mu..l of DAPI. DAPI labeling of nuclei was detected up to several days after a single application. No nuclear labeling was exhibited in cells of neighboring tissues. Methyl methanesulfonate (MMS)(10..mu..l) was applied to the anal lips of day-old chicks to study dose-response kinetics for mutagen targeting to DNA of dividing B-lymphocytes in the bursa. Since the mitotic index was found to be quite high (25-30%) in the bursa, chromosome analysis was used to assay for genome damage. Sister chromatid exchange frequencies of 3.9, 7.3, and 9.0 (baseline 2.5) per cell were obtained at MMS dosages per animal of 50 ..mu..g, 100..mu..g, and 200..mu..g, respectively. These results indicate the rapid and quantitative localization of DNA-binding chemicals to cells of the bursa, particularly the resident B-lymphocytes. The bursa should be a useful system for studying mutagen-DNA interactions in the differentiating B-lymphocyte and subsequent influences on the development of immunity and lymphoproliferative disease.
- Research Organization:
- Cornell Univ., Ithaca, NY
- OSTI ID:
- 6644761
- Journal Information:
- Environ. Mutagen.; (United States), Vol. 9:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
LYMPHOCYTES
CONFIGURATION INTERACTION
METHYL METHANESULFONATE
GENETIC EFFECTS
MUTAGENS
CELL DIFFERENTIATION
CHICKENS
DNA
FLUORESCENCE
INDOLES
NEONATES
ONCOGENES
ONCOGENIC VIRUSES
SISTER CHROMATID EXCHANGES
THYMIDINE
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
AZINES
AZOLES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIRDS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHROMOSOMAL ABERRATIONS
CONNECTIVE TISSUE CELLS
ESTERS
FOWL
GENES
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
LEUKOCYTES
LUMINESCENCE
MATERIALS
MICROORGANISMS
MUTATIONS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PARASITES
PYRIMIDINES
PYRROLES
RIBOSIDES
SOMATIC CELLS
SULFONIC ACID ESTERS
VERTEBRATES
VIRUSES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques