In vivo formation and persistence of DNA and protein adducts in mouse and rat skin exposed to (±)benzo[a]pyrene-4, 5-oxide
- 1 January 1986
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 7 (2) , 235-240
- https://doi.org/10.1093/carcin/7.2.235
Abstract
The objective of the present study was to compare DNA and protein adduct formation of benzo[a]pyrene-4, 5-oxide (BPO) in vivo and to determine the persistence of the adducts in both mouse and rat epidermis. (±)BPO at a dose of 100 nmol/mouse and 200 nmol/rat was topically applied to male Swiss mice and Wistar rats. Three hours after application, there was 3-fold less binding of BPO to mouse epidermal DNA than to rat epidermal DNA; inversely, the amount of BPO bound to mouse skin protein was 3.6 times higher than in rat skin protein. One and three weeks after application of BPO, persistence of 17–20% of the initial amount of BPO-DNA adducts and 2–4% of initial amount of BPO bound to protein was detected in both mouse and rat skin epidermis. H.p.l.c. analysis of the enzymatic hydrolysates of DNA from mouse and rat epidermis 3 h after application of BPO showed five distinct products: one early-eluting, two BPO-deoxyguanosine (dGuo) (ratio 1.5:1) and two BPO-deoxyadenosine (dAdo) adducts (ratio 2:1). The ratio of the total modified dGuo to the total modified dAdo was 2:1. The amount of total BPO-dGuo and BPO-dAdo adducts was 3.5 times greater in rat than in mouse epidermis. Persistence of the major BPO-dAdo adduct was observed in mouse and rat epidermal DNA, and 1 and 3 weeks after topical application of BPO there was a 6-fold greater amount of the persisting BPO-dAdo adduct in rat skin epidermis than in mouse skin epidermis (4.1 and 0.66 pmol/mg DNA, respectively). Minor amounts of the BPO-dGuo were found to persist in rat skin epidermis DNA.This publication has 16 references indexed in Scilit:
- The formation of benzo[a]pyrene—deoxyribonucleoside adducts in vivo and in vitroCarcinogenesis: Integrative Cancer Research, 1982
- Formation and excision of covalent deoxyribonucleic acid adducts of benzo[a]pyrene 4,5-epoxide and benzo[a]pyrenediol epoxide I in human lung cells A549Biochemistry, 1980
- Differences in mutagenicity and cytotoxicity of (+)- and (-)-benzo[a]pyrene 4,5-oxide: a synergistic interaction of enantiomers.Proceedings of the National Academy of Sciences, 1979
- The binding to mouse skin DNA of benzo[a]pyrene, its 7,8-diol and 7,8-diol-9,10-epoxides in relation to the tumourigenicity of these compoundsCancer Letters, 1979
- The in vitro and in vivo reaction at the N7-position of guanine of the ultimate carcinogen derived from benzo[a]pyreneChemico-Biological Interactions, 1979
- DOSE-RESPONSE FOR BENZO(A)PYRENE ADDUCTS IN MOUSE EPIDERMAL DNA1979
- Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.Proceedings of the National Academy of Sciences, 1978
- The covalent binding of polycyclic hydrocarbons to DNA in the skin of mice of different strainsInternational Journal of Cancer, 1978
- Specificity of human, rat and mouse skin epoxide hydratase towards K-region epoxides of polycyclic hydrocarbonsBiochemical Pharmacology, 1978
- Nucleoside adducts from the in vitro reaction of benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide or benzo[a]pyrene 4,5-oxide with nucleic acidsBiochemistry, 1977