In the sentence extracted from biomedical literature, identify all the chemical entities. The required answer format is the same sentence with HTML <span> tags to mark up specific entities. 
### Entity Markup Guides:
Use <span class="chemical"> to denote a chemical.

### Input Text: Throughout the study ( 20 weeks ) , deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX ; in these cases , histological investigations revealed marked changes in the heart that were consistent with DOX - induced cardiotoxicity .
### Output Text:
Throughout the study ( 20 weeks ) , deaths related to cardiotoxicity were observed only in animals that received either free <span class="chemical">DOX</span> or the mixture of <span class="chemical">HPMA</span> copolymer and free <span class="chemical">DOX</span> ; in these cases , histological investigations revealed marked changes in the heart that were consistent with <span class="chemical">DOX</span> - induced cardiotoxicity . 