Alkylation and arylation of bases can cause errors in replication. Some alkylating agents such as N-Nitrosamines may require the catalytic reaction of cytochrome-P450 for the formation of a reactive alkyl cation. N7 and O6 of guanine and the N3 and N7 of adenine are most susceptible to attack. N7-guanine adducts form the bulk of DNA adducts, but they appear to be non-mutagenic. Alkylation at O6 of guanine, however, is harmful because excision repair of O6-adduct of guanine may be poor in some tissues such as the brain. The O6 methylation of guanine can result in G to A transition, while O4-methylthymine can be mispaired with guanine. The type of the mutation generated, however, may be dependent on the size and type of the adduct as well as the DNA sequence.