Studies in human skin epithelial cell carcinogenesis
Metabolism and DNA adduct formation of benzo(a)pyrene (BP) by human epidermal keratinocytes pretreated with inhibitors or inducer of cytochrame P450 was studied. To study DNA adduct analysis, cultures were pretreated as described above, and then treated with non-radiolabeled BP. DNA was prepared from these cultures, digested to the nucleotide level, and /sup 32/P-postlabeled for adduct analysis. Cultures pretreated with BHA, 7,8-BF or disulfiralm formed significantly fewer BPDE I-dB adducts than non-pretreated cultures, while cultures pretreated with MeBHA formed more BPDE-I-dG adducts. MeBHA increased BP activation and adduct formation inhuman keratinocyte in cultures by inducing a specific isoenzyme of cytochrome P450 which preferentially increases the oxidative metabolism of BP to 7,8 diol BP and 7,8 diol BP to BPDE I. To approximate an in vivo human system, metabolism of BPDE I by human skin xenografts treated with cell cycles modulators was studied. When treated with BPDE I, specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the /sup 32/P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dG adducts were the major adducts.
- Research Organization:
- Ohio State Univ., Columbus (USA)
- OSTI ID:
- 6147810
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BENZOPYRENE
METABOLISM
DNA ADDUCTS
BIOSYNTHESIS
ANIMAL CELLS
CARCINOGENESIS
CELL CULTURES
EPIDERMIS
ISOENZYMES
MAN
METABOLIC ACTIVATION
PHOSPHORUS 32
TRACER TECHNIQUES
ADDUCTS
ANIMAL TISSUES
ANIMALS
AROMATICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CONDENSED AROMATICS
DAYS LIVING RADIOISOTOPES
EPITHELIUM
HYDROCARBONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
SKIN
SYNTHESIS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques