32P-postlabeling analysis of DNA adducts formed in vitro and in rat skin by methylenediphenyl-4,4'-diisocyanate (MDI).
Toxicol Lett
; 76(1): 17-26, 1995 Feb.
Article
in En
| MEDLINE
| ID: mdl-7701512
ABSTRACT
The 32P-postlabeling method was adapted for the detection of DNA adducts formed by methylenediphenyl-4,4'-diisocyanate (MDI). Incubation of the 3'-phosphates of the deoxyribosides of cytosine (C), adenine (A), guanine (G) and thymine (T) with MDI in Tris buffer resulted in the formation of 5, 7, 8, and 2 reaction products, respectively. Incubation of DNA with MDI resulted in detectable levels of 5, 2, and 1 adducts attributable to C, A, and G. Analysis of DNA isolated from the epidermis of rats treated dermally with 9 mg MDI showed an adduct pattern similar to the one seen in the in vitro DNA incubation. A total adduct level of 7 per 10(8) nucleotides was measured, the limit of detection was 2 adducts per 10(10) nucleotides. The data indicate that a minute fraction of MDI can reach DNA in vivo in a chemically reactive form. In comparison with the genotoxic skin carcinogen 7,12-dimethylbenz[a]anthracene on the other hand, the DNA-binding potency of MDI was more than 1000-fold lower.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin
/
Isocyanates
/
DNA Adducts
Limits:
Animals
Language:
En
Journal:
Toxicol Lett
Year:
1995
Document type:
Article